Search

Highlights • Extrapulmonary lymphangioleiomyomatosis is rare and can be associated with tuberous sclerosis. • Recognition of lymphangioleiomyomatosis is important for early disease screening and genetic testing. • Lymphangioleiomyomatosis in lower uterine segment is very rare and can be overlooked.

Aim of the work: This study aimed to assess long-term articular damage and function in rheumatoid arthritis (RA) patients in relation to the type of treatment. Early disease modifying anti-rheumatic drug (DMARD) therapy has not been evaluated in this study. Patients and methods: One hundred and fifty RA patients (141 females and 9 males) with disease duration more than five years and disease activity score-28 (DAS-28)

Follicular lymphoma (FL) is an indolent yet challenging disease. Despite a generally favorable response to immunochemotherapy regimens, a fraction of patients does not respond or relapses early with unfavorable prognosis. For the vast majority of those who initially respond, relapses will repeatedly occur with increasing refractoriness to available treatments. Addressing the clinical challenges in FL warrants deep understanding of the nature of treatment-resistant FL cells seeding relapses, and of the biological basis of early disease progression. Great progress has been made in the last decade in the description and interrogation of the (epi)genomic landscape of FL cells, of their major dependency to the tumor microenvironment (TME), and of the stepwise lymphomagenesis process, from healthy to subclinical disease and to overt FL. A new picture is emerging, in which an ever-evolving tumor-TME duo sparks a complex and multilayered clonal and functional heterogeneity, blurring the discovery of prognostic biomarkers, patient stratification and reliable designs of risk-adapted treatments. Novel technological approaches allowing to decipher both tumor and TME heterogeneity at the single-cell level are beginning to unravel unsuspected cell dynamics and plasticity of FL cells. The upcoming drawing of a comprehensive functional picture of FL within its ecosystem holds great promise to address the unmet medical needs of this complex lymphoma.

In the past 10 years, the healthcare industry is growing at a remarkable rate. The healthcare industry is generating enormous amounts of data in terms of volume, velocity, and variety. Big Data methodologies in healthcare can not only increase the business value but will also add to the improvement of healthcare services. Several techniques can be implemented to develop early disease diagnose systems and improve treatment procedures using detailed analysis over time. In such a situation, Big data Analytics proposes to connect intricate databases to achieve more useful results. In this chapter, we will discuss the procedure of big data analytics in the healthcare sector with some practical applications along with its challenges. We will also have a look at the various big data techniques and their tools for implementation. We conclude this chapter with a discussion on potential opportunities for analytics in the healthcare sector.

Improving diagnostics has been one of the most important challenges facing health systems in recent years, due to innovation and scientific research, image classification techniques, medical information management systems brought about by health technology, and developments never seen before that enable major breakthroughs in the areas of prevention, early disease detection, and disease control. Blood is investigated through blood count, which is subordinate to manual and/or automated procedures. This reliance on medical fields for new innovations directs this chapter to the development of a deep learning framework for classifying white cell subtypes in digital images that fits the criteria for reliability and efficiency of blood cell detection, making the methodology more accessible to diverse populations. Because laboratory medical examinations are often costly and inaccessible to populations of underdeveloped and developing countries, it is of great importance to create tools that facilitate the obtaining of medical reports at low cost and with high reliability. For this, Python using a Jupyter notebook was developed and experiments were conducted using a dataset containing 12,500 digital images of human blood smear fields comprising nonpathological leukocytes. As a result, the accuracy of the approach was 86.17%, demonstrating the high reliability of the methodology. Therefore the algorithm is considered a reliable, accurate, and inexpensive method and can be employed as the third most practicable procedure for blood counts for often underprivileged people of developing and underdeveloped countries.

Microfluidics is an emerging field in diagnostics that allows for extremely precise fluid control and manipulation, enabling rapid and high-throughput sample processing in integrated micro-scale medical systems. These platforms are well-suited for both standard clinical settings and point-of-care applications. The unique features of microfluidics-based platforms make them attractive for early disease diagnosis and real-time monitoring of the disease and therapeutic efficacy. In this chapter, we will first provide a background on microfluidic fundamentals, microfluidic fabrication technologies, microfluidic reactors, and microfluidic total-analysis-systems. Next, we will move into a discussion on the clinical applications of existing and emerging microfluidic platforms for blood analysis, and for diagnosis and monitoring of cancer and infectious disease. Together, this chapter should elucidate the potential that microfluidic systems have in the development of effective diagnostic technologies through a review of existing technologies and promising directions.

Nanocontainers embody a “compartmentalized” structural archetype with the potential to operate on a dimensional scale that can either assimilate or be integrated within bio-driven processes. With expected improvements in sensitive diagnostic assays for early disease detection (e.g., CTCs or circulating tumor cells), this has important implications for developing drug delivery technologies to areas of small confinement in the body. Functionalized nanocontainers with tunable surface properties can help stabilize and release therapeutic chemical and biological drugs within nano- and sub-nano spaced cavities. Here, we discuss recent developments in the field of “nanocontainers” that show promise for addressing some of the more challenging aspects of drug therapeutics.

The free-living amoebae are thermophilic organisms that may play an increasing role among diseases of a warming world. They are uncommon, accidental, yet high consequence pathogens, with differing pathologic syndromes. New prospects for diagnosis and life-saving treatment make early disease recognition imperative. We review the three most commonly diagnosed species that infect humans: Naegleria fowleri, Acanthamoeba species, and Balamuthia mandrillaris. Keywords: Amoeba, Ameba, Naegleria, Acanthamoeba, Balamuthia, Meningitis, Encephalitis

Multiparametric myocardial characterization with T1, T2, and extracellular volume (ECV) promises to play a useful role in a variety of clinical settings. Diffuse myocardial processes can be detected and quantified—particularly edema, infiltration and storage disorders with large disease-related changes, and diffuse fibrosis where measurement is harder but the potential impact larger. This has added a new dimension to the understanding and assessment of various myocardial diseases. Multiparametric mapping promises to detect early disease, quantify disease severity, and provide prognostic insights into certain conditions. For certain diseases, there is the potential to define new disease categories (e.g., global myocarditis). Using the ECV, by dividing the myocardium into the cellular and interstitial compartments, hypertrophy is potentially divided into adaptive and maladaptive. It has the potential to be a surrogate marker in drug development trials to monitor therapeutic response and be a prognostic marker in certain diseases. This is an evolving field, and stability in sequence design as well as standardization is required for routine use in clinical practice.

The primary advance in imaging of axial spondyloarthritis (axSpA) over the past decade has been the widespread application of magnetic resonance imaging for diagnostic evaluation of axSpA and its incorporation into classification criteria that define a patient with this disease. There is now greater understanding of the full spectrum of structural lesions and their temporal relationship to inflammation. Low-radiation computed tomography of the sacroiliac (SI) joints is emerging as an additional tool to assess structural lesions in early disease, especially erosions, whereas assessment of the spine may enhance detection of new bone formation in advancing disease.

Pancreatic cancer remains one of the most intractable cancers, with a dismal prognosis reflected by a 5-year survival of ~6%. Since early disease symptoms are undefined and specific biomarkers are lacking, about 80% of patients present with advanced, inoperable tumors that represent a daunting challenge. Despite many clinical trials, no single chemotherapy agent has been reliably associated with objective response rates above 10% or median survival longer than 5 to 7 months. Although combination chemotherapy regimens have in recent years provided some improvement, overall survival (8-11 months) remains very poor. There is therefore a critical need for novel therapies that can improve outcomes for pancreatic cancer patients. Here, we present a summary of the current therapies used in the management of advanced pancreatic cancer and review novel therapeutic strategies that target tumor biomarkers. We also describe our recent research using phosphatidylserine-targeted saposin C–coupled dioleoylphosphatidylserine nanovesicles for imaging and therapy of pancreatic cancer.

This chapter summarizes the advances in diagnosis of Parkinson's disease (PD) that were encapsulated in new International Parkinson Disease and Movement Disorders Society diagnostic criteria for PD. Numerous changes in our understanding of PD have occurred, including our understanding of the nonmotor profile of disease, the recognition of PD as a synucleinopathy, identification of genetic causes, novel hypotheses about spread of disease, etc. These have been reflected in a new definition of PD, which includes a clinicogenetic subtype of PD, removes dementia with Lewy Bodies as an exclusion criterion against PD, and recognizes multiple stages of early disease. The Clinical Diagnostic Criteria for PD reflect these changes and offer a new standardized diagnostic method for use in clinical research and even clinical practice. The criteria for prodromal PD use a method not seen in previous diagnostic criteria; they rely upon published studies of PD predictors to calculate the probability that any individual will develop PD. The field of PD is constantly advancing, and our methods of diagnosis need to advance with it; one hopes for a future filled with constant revisions and updates in our diagnostic methodology.

The increase in lifespan during the last 50 years, mainly in developed countries, has originated a progressive elevation in the incidence of chronic neurodegenerative disorders, for which aging is the key risk factor. This fact will definitively become the major biomedical challenge during the present century, in part because the expectation of a persisting elevation in the population older than 65 years over the whole population and, on the other hand, because the current lack of efficacious therapies to control these disorders despite years of intense research. This chapter will address this question and will stress the urgency of developing better neuroprotective and neurorepair strategies that may delay/arrest the progression of these disorders, reviewing the major needs to solve the causes proposed for the permanent failures experienced in recent years, e.g., to develop multitarget strategies, to use more predictive experimental models, and to identify early disease biomarkers. This chapter will propose the cannabinoids and their classic (e.g., endocannabinoid receptors and enzymes) and nonclassic (e.g., peroxisome proliferator-activated receptors, transcription factors) targets as a useful strategy for developing novel therapies for these disorders, based on their broad-spectrum neuroprotective profile, their activity as an endogenous protective system, the location of the endocannabinoid targets in cell substrates critical for neuronal survival, and their ability to serve for preservation and rescue, but also for repair and/or replacement, of neurons and glial cells against cytotoxic insults.

Acute joint injury predisposes to OA, and is an ideal setting in which to study early disease pathogenesis. We have shown that an immediate inflammatory response occurs in connective tissues after injury, and a discrete group of mRNAs is up-regulated within hours of medial meniscal destabilisation (DMM) of the mouse joint. Some of this molecular response appears necessary for subsequent OA. We investigated a) whether these same molecules were up-regulated in the joint, and in the blood in the analogous human setting of acute knee injury, and b) how this molecular response varies, between individuals and over time.

Pediatric-onset multiple sclerosis (MS) represents an important unmet clinical need as well as a unique opportunity to study early disease mechanisms. While some features (including degree of focal–inflammatory activity, apparent recovery from acute relapse) differ between pediatric- and adult-onset MS, shared genetic and environmental risk factors across the age spectrum suggest that mechanisms underlying MS development in children are in essence the same as in adults, and that any differences may be more likely to reflect manifestation of the same disease in younger and still maturing immune and nervous systems. The shorter interval between biological and clinical onset in children with MS limits the number of irrelevant exposures or biological abnormalities that may emerge as a consequence (rather than cause) of disease. Here, we review genetic and environmental risk factors implicated in the pediatric MS population and summarize emerging insights into early humoral and cellular immune targets and mechanisms involved in disease pathogenesis.

Osteoarthritis is a heterogeneous disorder. The goals of this review are (1) To stimulate use of standardized nomenclature for osteoarthritis (OA) that could serve as building blocks for describing OA and defining OA phenotypes, in short to provide unifying disease concepts for a heterogeneous disorder; and (2) To stimulate establishment of ROAD (Risk of Osteoarthritis Development) and ROAP (Risk of Osteoarthritis Progression) tools analogous to the FRAX™ instrument for predicting risk of fracture in osteoporosis; and (3) To stimulate formulation of tools for identifying disease in its early preradiographic and/or molecular stages -- REDI (Reliable Early Disease Identification). Consensus around more sensitive and specific diagnostic criteria for OA could spur development of disease modifying therapies for this entity that has proved so recalcitrant to date. We fully acknowledge that as we move forward, we expect to develop more sophisticated definitions, terminology and tools.

Hyperlipidemia is an important public health problem with increased incidence and prevalence worldwide. Current clinical biomarkers, triglyceride, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol lack the necessary specificity and sensitivity and only increase significantly after serious dyslipidemia. Therefore, sensitive biomarkers are needed for hyperlipidemia. Hyperlipidemia-specific biomarkers would improve clinical diagnosis and therapeutic treatment at early disease stages. The aim of metabolomics is to identify untargeted and global small-molecule metabolite profiles from cells, biofluids, and tissues. This method offers the potential for a holistic approach to improve disease diagnoses and our understanding of underlying pathologic mechanisms. This review summarizes analytical techniques, data collection and analysis for metabolomics, and metabolomics in hyperlipidemia animal models and clinical studies. Mechanisms of hypolipemia and antilipemic drug therapy are also discussed. Metabolomics provides a new opportunity to gain insight into metabolic profiling and pathophysiologic mechanisms of hyperlipidemia.

Nuclear imaging techniques that include positron emission tomography (PET) and single-photon computed tomography have found great success in the clinic because of their inherent high sensitivity. Radionuclide imaging is the most popular form of imaging to be used for molecular imaging in oncology. While many types of molecules have been used for radionuclide-based molecular imaging, there has been a great interest in developing newer nanomaterials for use in clinic, especially for cancer diagnosis and treatment. Nanomaterials have unique physical properties which allow them to be used as imaging probes to locate and identify cancerous lesions. Over the past decade, a great number of nanoparticles have been developed for radionuclide imaging of cancer. This chapter reviews the different kinds of nanomaterials, both organic and inorganic, which are currently being researched for as potential agents for nuclear imaging of variety of cancers. Several radiolabeled multifunctional nanocarriers have been extremely successful for the detection of cancer in preclinical models. So far, significant progress has been achieved in nanoparticle structure design, in vitro/in vivo trafficking, and in vivo fate mapping by using PET. There is a great need for the development of newer nanoparticles, which improve active targeting and quantify new biomarkers for early disease detection and possible prevention of cancer.

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common inherited neuromuscular disease, with an epigenetic basis linked to contractions or hypomethylation of the chromosome 4q subtelomere. Efforts to understand chromatin alterations in this region have yielded several interesting models of the disorder. This chapter summarizes the genetic and epigenetic etiology of FSHD and the search for candidate genes, with an emphasis on recent discoveries. It also seeks to highlight current therapeutic strategies and future directions for the field. In particular, there is a need for large, well-controlled studies to identify consistent biomarkers of early disease pathology.

Purpose: To compare retinal thickness and choroidal thickness at increasing retinal eccentricity in individuals with early age-related macular degeneration (AMD) and in healthy controls using enhanced choroidal penetration, 3-dimensional optical coherence tomography at 1060 nm.\ud \ud Design: Cross-sectional study.\ud \ud Methods: Individuals with early AMD (n = 16; mean age, 71.6 ± 8.5 years) and a comparison group of healthy controls (n = 16; 67.6 ± 5.4 years) were recruited. Three-dimensional (20 degrees × 20 degrees) long-wavelength optical coherence tomography (1060 nm) images (approximately 8-μm axial resolution; 47 000 A scans/second, centered on the fovea) were obtained from all participants after pupil dilation. Retinal thickness was measured between the inner limiting membrane and the retinal pigment epithelium. Choroidal thickness was measured between the retinal pigment epithelium and the choroid–scleral interface. Thickness measurements were obtained subfoveally and at 0.5-mm intervals to a maximum of 2.0 mm nasally, temporally, superiorly, and inferiorly. The main outcome measures were retinal and choroidal thickness (measured in micrometers) at different eccentricities on vertical and horizontal meridians.\ud \ud Results: Mean retinal thickness was reduced significantly in the group of participants with early AMD compared with the control group at multiple locations within 2.0 mm of the fovea. This difference was most significant at the fovea, where the mean retinal thickness of the early AMD group was 179 ± 27 μm and that of the control group was 202 ± 18 μm (P = .008). There was no significant difference in choroidal thickness between groups at any location.\ud \ud Conclusions: Retinal thickness is reduced in early AMD, but choroidal thickness seems to be unaffected by the early disease process.

Publisher Summary This chapter discusses the status of cancer treatment using antibody-drug conjugates. In parallel with definition of differences between normal and neoplastic cells, is the development of reagents with a high degree of selectivity for targets on the surface and within neoplastic cells. Over the past years, considerable interest has been focused on targeting systems designed to permit selective delivery of drugs, radioisotopes, and toxins to tumors for both diagnosis and therapy and a great deal of this research has been performed utilizing antibodies as carriers. As vehicles for carrying cytotoxic agents to tumors, antibodies have the greatest potential; however, a number of other possible carriers have been investigated. The conjugation of isotopes to antibodies employ relatively simple procedures, and the conjugation of toxins is only slightly more difficult using disulfide bonding of toxin to antibody. Conjugation difficulties aside, isotopes have a finite half–life, are difficult to handle, and may damage surrounding tissues, although for some isotopes this may be useful for destroying antigen-negative cells within the tumor mass. Large tumors have proved difficult to eradicate using antibody-drug conjugates, mainly because of poor tumor access. Immunoconjugates will find their place in the treatment of cancer together with surgery, radiotherapy, and conventional treatment particularly in patients with minimal and microscopic disease. Phase II/III clinical trials involve patients with early disease, and immunotherapeutic protocols are instituted after surgery for the treatment of microscopic disease in an adjuvant setting.