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The growing prevalence of nonalcoholic fatty liver disease (NAFLD), determined by fatty liver index, amongst young adults in the United States. A 20-year experience
No full textAim: The Global burden of nonalcoholic fatty liver disease (NAFLD) has significantly increased recently, with its prevalence mirroring increasing obesity and diabetes. However, population-specific evidence for young adults remains limited. Herein, we provide a 20-year trend analysis of NAFLD in young adults and examine factors associated with NAFLD and major adverse cardiovascular events (MACE) prevalence.Methods: This study uses data from the United States National Health and Nutrition Examination Survey (NHANES) 1999-2018. Fatty liver was examined with the fatty liver index (FLI) and United States-FLI (US-FLI), and advanced fibrosis was examined with the fibrosis-4 index. Clustered multivariate logistic regression analysis on the year of study was applied to obtain odds ratios (OR) for the estimation of events.Results: 13.31% (95%CI: 12.71% to 13.94%) of young adults had NAFLD. The prevalence increased from 9.98% in 1999 to 19.49% in 2018, with a statistically significant trend (P < 0.001). 9.52% and 5.29% of patients have clinically significant and advanced fibrosis, respectively. In multivariate analysis, diabetes (3.48, 95%CI: 2.37 to 5.11), hypertension (2.03, 95%CI: 1.62 to 2.55), elevated body mass index (1.22, 95%CI: 1.20 to 1.23, P < 0.001) significantly increases odds of NAFLD. The largest increase in odds was related to obesity (OR: 21.61, 95%CI: 16.95 to 27.55, P < 0.001). Young adults with NAFLD had a borderline non-significant increase in the prevalence of MACE compared to individuals without NAFLD (OR: 1.603, 95%CI: 0.949 to 2.708, P = 0.078).Conclusion: The rising prevalence of NAFLD in young adults depicts the changing landscape of NAFLD and its association with a significant increase in MACE. The challenge of effective risk stratification and education of these individuals remains
Diminished function of cytotoxic T- and NK- cells in severe alcohol-associated hepatitis
No full textAim: Metabolic liver diseases, including alcohol- and non-alcoholic fatty liver diseases (ALD/NAFLD), are characterized by inflammation and decreased ability to prevent infections. Patients with severe alcohol-associated hepatitis (sAH) are particularly susceptible to infections while undergoing treatment with steroids. Understanding the immunological mechanisms for these responses is critical to managing the treatment of patients with metabolic liver diseases. Cytotoxic NK cells and CD8 T cells, using cytolytic granules, serve an important immunological role by killing infected cells, including monocytes. However, patients with sAH have dysfunctional NK cells, which cannot kill target cells, though the mechanism is unknown.Method: We performed an exploratory study using single-cell RNA-seq (scRNA-seq) (n = 4) and multi-panel intracellular flow cytometry (n = 7-8 for all patient groups) on PBMCs isolated from patients with sAH and healthy controls (HC). Results: ScRNA-seq revealed receptors in NK cells and CD8 T cells required for cytotoxic cell recognition of activated monocytes were downregulated in patients with sAH compared to healthy controls. Granulysin was the most downregulated gene in both NK cells and effector CD8 T cells. In NK cells from HC, expression of granulysin, perforin, and granzymes A and B was highly correlated; however, in sAH, these genes lost coordinate expression, indicative of dysfunctional cytolytic granule formation. Finally, the expression of cytolytic granule proteins in NK cells was decreased from sAH, indicating reduced cytolytic granules.Conclusion: Together, these results suggest a loss of cytotoxic cell function in PBMCs from sAH that may contribute to a decreased ability to communicate with other immune cells, such as monocytes, and prevent the killing of infected cells, thus increasing the risk of infection
Follicular lymphoma: the diminishing role of chemotherapy
No full textFollicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma, accounting for 70% of cases in Western countries. Despite this unique name, FL is an extremely heterogeneous disease, both clinically and biologically. The basis of FL heterogeneity lies in the different biological pathways which can be activated, because of the variety of gene mutations that can occur. Today, there is a growing interest in the knowledge of these activated pathways, which is also testified by the presence of a new model that incorporates FL mutations to define patient’s prognosis (m7-FLIPI). These evaluations are also appealing because of the recent possibility of using “targeted therapies”. Targeted therapies are new tools, currently applicable in the setting of relapse/refractory (R/R) disease, where we can find a great variety of “chemo-free” combinations. As in other hematologic malignancies, “cellular therapy” enriches FL drug scenario, including T-cell dependent bispecific antibodies and chimeric antigen receptor (CAR) T-cell. Since FL heterogeneity is the basis of the difference in therapeutic efficacy and disease course among patients, the hope for the future is to understand FL biology more deeply, to better comprehend how to obtain more representative samples and pre-treatment prognostic information in order to individualize the treatment strategy as early as frontline therapy
A shifting adversary: control of pancreatic cancer transcriptomic subtypes
No full textCellular plasticity, the dynamic ability of cells to adopt distinct transcriptional states, plays a well-known role in the pancreas during the initiation of pancreatic ductal adenocarcinoma (PDA), the most common form of pancreatic cancer. It is now becoming clear that plasticity also plays an important role after the emergence of PDA. PDA is composed of two major transcriptional subtypes, classical and basal-like, with important biological differences. Recent work has indicated that individual tumors can be comprised of cells of each subtype, and that tumor subtype can change during the evolution of a tumor. This suggests that PDA cells can transit between transcriptional states, with important implications for disease progression. This review discusses what is currently known about inter-subtype plasticity and how this process is controlled
The peripheral T-cell lymphoma: can we pivot from the chemotherapy-predicated paradigm?
No full textPeripheral T-cell lymphomas (PTCL) are uncommon and aggressive diseases that are difficult to study. Combination chemotherapy such as cyclophosphamide, doxorubicin, vincristine, and prednisone has been the mainstay of treatment for almost 30 years, but outcomes remain poor. The development of new targeted therapies is changing the landscape of how we treat patients with these difficult diseases. For instance, the addition of brentuximab vedotin to combination chemotherapy enhanced the outcomes in patients with CD30-positive anaplastic large cell lymphomas, but there is still a need for better therapies in the other numerous subtypes. Here we discuss the data for the existing treatment paradigm of PTCL as well as the merits of shifting toward a chemotherapy-free approach
Role of myeloid cells in the tumor microenvironment
No full textThe dynamic interplay between tumor cells and immune cells in the microenvironment plays a crucial role in determining disease severity and therapeutic outcome in cancer. Myeloid cells are the most abundantly available cell population in the tumor microenvironment. Myeloid cells have been shown to exist in diverse phenotypes and play both antitumoral and protumoral roles in cancer. Understanding the biology of myeloid cells can lay the foundation for the development of therapeutic strategies aimed at enhancing the antitumoral role of myeloid cells. This article presents an overview of the role of myeloid cells in tumor development and various mechanisms by which myeloid cells aid tumor progression. Existing drugs against cancer that utilize myeloid cells and the role of myeloid cells in drug resistance are also discussed
Telemedicine for sarcoma patient care
No full textTelemedicine is being incorporated into routine healthcare, including oncology. The integration of telemedicine with patient electronic medical records and the adoption of virtual provider-patient encounters was accelerated by the SARS-CoV2 worldwide pandemic. Although telemedicine has existed for more than 50 years, the impact of telemedicine on patient care and health outcomes is relatively understudied, and little research has been conducted on telehealth in the care of patients with sarcoma. This review discusses the potential applications of telemedicine to the care of patients with sarcoma and some of the data available on patient and provider preferences for telemedicine vs. in-person healthcare encounters. Some of the areas of care in which greater adoption of telemedicine may be beneficial to patients with sarcoma are also discussed
The role of radiation therapy in the management of primary thymic epithelial neoplasms
No full textTherapeutic radiation plays an important role in the management of thymoma and thymic carcinoma. These two tumor types differ substantially in their aggressiveness and prognosis. The most pressing issue in radiotherapy is which thymoma and thymic carcinoma patients need radiation. Given that these are rare cancers, few randomized trials have been published. Controversy remains regarding which patients benefit from adjuvant radiation therapy. Existing literature spans patients treated over nearly 50 years, during which time radiation therapy has evolved from rudimentary 2-dimensional based planning to conformal 3-dimensional planning to yet more conformal dose painting techniques such as intensity-modulated radiation therapy and proton therapy. If the effect of radiation is small and the natural history of a disease long, as is the case for stage I favorable histology thymoma, then differences in techniques and toxicities may have as much of an impact as whether radiation was given or not
Cholangiocarcinoma: early detection and screening in high-risk population
No full textCholangiocarcinoma (CCA) is a highly lethal malignancy that comprises approximately 15% of all the primary liver tumors and 3% of gastrointestinal cancers. Diagnosis is often done when the disease is already at advanced stages, resulting in poor outcomes. Prevention of risk factors and early diagnosis are the cornerstones for improving survival. Early diagnosis is feasible in the setting of surveillance programs in patients at high risk of CCA such as patients with primary sclerosing cholangitis. Regrettably, surveillance of CCA in this population is hampered by the low diagnostic accuracy of current tumor markers at earlier stages, the difficulties of imaging techniques for the differential diagnosis between benign and malignant biliary strictures, and the need for invasive procedures for diagnostic confirmation. In this review we discuss the rationale for surveillance of CCA in high-risk populations, particularly patients with primary sclerosing cholangitis, the recommended tools for surveillance and diagnostic work-up, and future perspectives
The duration of the conventional chemoembolization for hepatocellular carcinoma: factors affecting the procedural time
No full textAim: The present study evaluated the duration of chemoembolization in patients with hepatocellular carcinoma, analyzing possible factors affecting the procedural time.Methods: In total, 175 patients who underwent chemoembolization have been prospectively enrolled. The procedural length was considered the time between the insertion and the removal of the angiographic sheath. The features related to the tumor burden and angiographic procedures, which could be related to the procedural time, were recorded.Results: The chemoembolization time resulted in a mean of 58.1 min. The longer procedural time was associated with a number of nodules treated per patient ≥ 2 (P < 0.001), a number of segments with nodules ≥ 2 (P < 0.001), the presence of more than 1 nodule in the same segment (P < 0.001), the location of the tumor in the left lobe (P = 0.001), the exclusion from the Milan criteria (P < 0.001), and a number of segments treated ≥ 2 (P < 0.001). Only the number of nodules treated per patient resulted significantly in multivariate analysis (OR 2.927, 95%CI: 2.015-4.251, P < 0.001).Conclusion: The factors related to longer procedural time are the number of nodules treated ≥ 2, the number of segments with nodules ≥ 2, the involvement of the left lobe, the tumor burden outside the Milan criteria, and the number of segments treated ≥ 2. All these characteristics, known in the pre-procedural phase, represent useful tools for a correct planning of the angiographic room’s workflow during the pandemic era as well as in the future to reduce downtime and increase productivity
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