Objectives: There are only sporadic reports on the clinical behavior and appropriate treatment of anaplastic seminoma. This retrospective study summarizes our experience with the anaplastic variant of classical (typical) seminoma.
Methods: Between 1986 and 2006, seven anaplastic seminoma patients were staged and treated at the Northern Israel Oncology Center. Staging procedures included meticulous physical and neurological examinations, complete blood count, full biochemistry profile, specific tumor markers, testicular ultrasound, and other radiological measures. All patients underwent inguinal orchiectomy and were staged properly. Six patients had stage I disease, and one patient had stage IIA disease. Patients were irradiated with doses ranging from 2,500 to 3,000 cGy, and the stage IIA patient received an additional 1,000 cGy boost to radiographically involved lymph nodes.
Results: After a mean follow-up of 11 years, six patients are alive with no evidence of disease. One patient died due to an unknown, non-oncological, cause, unrelated to his previous testicular tumor, while in complete remission.
Conclusions: Despite the low patient numbers and the retrospective nature of our study, it can be concluded that radiotherapy treatment for early-stage anaplastic seminoma patients might achieve the same excellent survival as for classical seminoma. However, the general consensus achieved through large-scale studies suggests that active surveillance should be offered to all stage I seminoma patients, regardless of the pathologic variant.
Despite its status as a world leader in treatment innovation and medical education, a quality chasm exists in American health care. Care fragmentation and poor coordination contribute to expensive care with highly variable quality in the United States. The rising costs of health care since 1990 have had a huge impact on individuals, families, businesses, the federal and state governments, and the national budget deficit. The passage of the Affordable Care Act represents a large shift in how health care is financed and delivered in the United States. The objective of this review is to describe some of the economic and social forces driving health care reform, provide an overview of the Patient Protection and Affordable Care Act (ACA), and review model cardiovascular quality improvement programs underway in the state of Michigan. As health care reorganization occurs at the federal level, local and regional efforts can serve as models to accelerate improvement toward achieving better population health and better care at lower cost. Model programs in Michigan have achieved this goal in cardiovascular care through the systematic application of evidence-based care, the utilization of regional quality improvement collaboratives, community-based childhood wellness promotion, and medical device-based competitive bidding strategies. These efforts are examples of the direction cardiovascular care delivery will need to move in this era of the Affordable Care Act.
Squamous cell carcinoma of the larynx continues to be the commonest head and neck cancer in many Western countries. The larynx plays a key role for many essential functions, including breathing, voice production, airway protection, and swallowing. The goals of laryngeal cancer treatment are thus to provide best possible oncologic control, while optimizing functional outcomes.
In recent decades, the treatment paradigm for advanced laryngeal cancer has shifted from one of primary surgery (total laryngectomy) as gold standard, toward non-surgical organ-preserving treatment using radiotherapy or chemoradiotherapy. However, concerns have emerged regarding functional outcomes after chemoradiotherapy, as well as possible decreased overall survival in patients with laryngeal cancer.
The purpose of the present review is to review surgical and non-surgical options for treatment of advanced laryngeal cancer, as well as the evidence supporting each of these.
Thrombotic microangiopathies (TMAs) comprise a group of distinct disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and microvascular thrombosis. For many years distinction between these TMAs, especially between thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), remained purely clinical and hard to make. Recent discoveries shed light on different pathogenesis of TTP and HUS. Ultra-large von Willebrand factor (UL-VWF) platelet thrombi, resulting from the deficiency of cleavage protease which is now known as ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), were found to cause TTP pathology, while Shiga toxins or abnormalities in regulation of the complement system causes microangiopathy and thrombosis in HUS. TMAs may appear in various conditions such as pregnancy, inflammation, malignancy, or exposure to drugs. These conditions might cause acquired TTP, HUS, or other TMAs, or might be a trigger in individuals with genetic predisposition to ADAMTS-13 or complement factor H deficiency. Differentiation between these TMAs is highly important for urgent initiation of appropriate therapy. Measurement of ADAMTS-13 activity and anti-ADAMTS-13 antibody levels may advance this differentiation resulting in accurate diagnosis. Additionally, assessment of ADAMTS-13 levels can be a tool for monitoring treatment efficacy and relapse risk, allowing consideration of therapy addition or change. In the past few years, great improvements in ADAMTS-13 assays have been made, and tests with increased sensitivity, specificity, reproducibility, and shorter turnaround time are now available. These new assays enable ADAMTS-13 measurement in routine clinical diagnostic laboratories, which may ultimately result in improvement of TMA management.
Pregnancy is a physiological hypercoagulable state, preparing the mother for the hemostatic challenge of delivery. However, this is associated with an increased risk of venous thrombosis and placenta-mediated complications, which present major challenges for mother and fetus. Although these conditions are heterogeneous in their pathophysiology, hereditary and acquired thrombophilia has been associated with recurrent pregnancy loss and gestational vascular complications, such as early-onset pre-eclampsia and placental abruption. Prevention of such placenta-mediated complications, which collectively complicate up to 15% of pregnancies, is a major issue for women’s health. Prospective interventional studies stratified by current knowledge of pathophysiological mechanisms related to placental and systemic hemostatic alterations will impact on the management of pregnancies at risk of these complications.
Venous thromboembolism (VTE), the third most frequent acute cardiovascular syndrome, may cause life-threatening complications and imposes a substantial socio-economic burden. During the past years, several landmark trials paved the way towards novel strategies in acute and long-term management of patients with acute pulmonary embolism (PE). Risk stratification is increasingly recognized as a central cornerstone for an adequate diagnostic and therapeutic management of the highly heterogeneous population of patients with acute PE. Recently published European Guidelines emphasize the importance of clinical prediction rules in combination with imaging procedures (assessment of right ventricular function) and laboratory biomarkers (indicative of myocardial stress or injury) for identification of normotensive PE patients at intermediate risk for an adverse short-term outcome. In this patient group, systemic full-dose thrombolysis was associated with a significantly increased risk of intracranial bleeding, a complication which discourages its clinical application unless hemodynamic decompensation occurs. A large-scale clinical trial program evaluating new oral anticoagulants in the initial and long-term treatment of venous thromboembolism showed at least comparable efficacy and presumably increased safety of these drugs compared to the current standard treatment. Research is continuing on catheter-directed, ultrasound-assisted, local, low-dose thrombolysis in the management of intermediate-risk PE.
In Alzheimer’s disease (AD), premature demise of acetylcholine-producing neurons and the consequent decline of cholinergic transmission associate with the prominent cognitive impairments of affected individuals. However, the enzymatic activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are altered rather late in the disease progress. This raised questions regarding the causal involvement of AChE and BChE in AD. Importantly, single nucleotide polymorphisms (SNPs), alternative splicing, and alternate promoter usage generate complex expression of combinatorial cholinesterase (ChE) variants, which called for testing the roles of specific variants in AD pathogenesis. We found accelerated amyloid fibril formation in engineered mice with enforced over-expression of the AChE-S splice variant which includes a helical C-terminus. In contrast, the AChE-R variant, which includes a naturally unfolded C-terminus, attenuated the oligomerization of amyloid fibrils and reduced amyloid plaque formation and toxicity. An extended N-terminus generated by an upstream promoter enhanced the damage caused by N-AChE-S, which in cell cultures induced caspases and GSK3 activation, tau hyperphosphorylation, and apoptosis. In the post-mortem AD brain, we found reduced levels of the neuroprotective AChE-R and increased levels of the neurotoxic N-AChE-S, suggesting bimodal contribution to AD progress. Finally, local unwinding of the α-helical C-terminal BChE peptide and loss of function of the pivotal tryptophan at its position 541 impair amyloid fibril attenuation by the common BChE-K variant carrying the A539T substitution, in vitro. Together, our results point to causal yet diverse involvement of the different ChEs in the early stages of AD pathogenesis. Harnessing the neuroprotective variants while reducing the levels of damaging ones may hence underlie the development of novel therapeutics.
KEY WORDS: Acetylcholinesterase, Alzheimer’s disease, apoptosis, beta-amyloid, butyrylcholinesterase
Advancements in computers, prototyping, and imaging, especially over the last 10 years, have permitted the adoption of three-dimensional imaging protocols in the health care field. In this article, the authors present an integrated simulation system for craniofacial surgical planning and treatment. Image fusion technology, which involves combining different imaging modalities, was utilized to create a realistic prototype and virtual image that can be manipulated in real time. The resultant data can then be shared over the Internet with distantly located practitioners.
Objective. To understand high-performing front-line employees’ values as reflected in their narratives of day-to-day interactions in a large health care organization.
Methods. A total of 150 employees representing various roles within the organization were interviewed and asked to share work-life narratives (WLNs) about value-affirming situations (i.e. situations in which they believed their actions to be fully aligned with their values) and value-challenging situations (i.e. when their actions or the actions of others were not consistent with their values), using methods based on appreciative inquiry.
Results. The analysis revealed 10 broad values. Most of the value-affirming WLNs were about the story-teller and team providing care for the patient/family. Half of the value-challenging WLNs were about the story-teller or a patient and barriers created by the organization, supervisor, or physician. Almost half of these focused on “treating others with dis/respect”. Only 15% of the value-challenging WLNs contained a resolution reached by the participants, often leaving them describing unresolved and frequently negative feelings.
Conclusions. Appreciative inquiry and thematic analysis methods were found to be an effective tool for understanding the important and sometimes competing role personal and institutional values play in day-to-day work. There is remarkable potential in using WLNs as a way to surface and reinforce shared values and, perhaps more importantly, respectfully to identify and discuss conflicting personal and professional values.
Cardiovascular disease is the most prevalent disease mainly in the Western society and becoming the leading cause of death worldwide. Standard methods by which health care providers screen for cardiovascular disease have only minimally reduced the burden of disease while exponentially increasing costs. As such, more specific and individualized methods for functionally assessing cardiovascular threats are needed to identify properly those at greatest risk, and appropriately treat these patients so as to avoid a fate such as heart attack, stroke, or death. Currently, endothelial function testing—in both the coronary and peripheral circulation—is well-established as being associated with the disease process and future cardiovascular events. Improving such testing can lead to a reduction in the risk of future events. Combining this functional assessment of vascular fitness with other, more personalized, testing methods should serve to identify those at the greatest risk of cardiovascular disease earlier and subsequently reduce the affliction of such diseases worldwide.
