Purpose. This is a population study of patients who were treated for vulvar cancer in a tertiary center in northern Israel, aimed to report clinical findings, treatment, and outcome.
Methods. A retrospective chart review of all medical records of consecutive patients who were treated for vulvar cancer in the years 1993–2012 was conducted. Data extracted from the medical records included demographics, histology, size of lesion, stage of disease at diagnosis, type of treatment, radiation dose, follow-up, recurrence, and survival.
Results. The study included 44 patients with a median age of 69.8 years (range, 42–93 years). Thirty-five (79.5%) of the patients were of Jewish descent, five were Arabic, and four were of other descent. The most common histology type was squamous cell carcinoma in 35 (79.5%) patients. Most patients were staged FIGO II–III at time of diagnosis. Surgery was the most common primary treatment modality (54.2%). Twenty-three (52.2%) patients had recurrent disease. Older age and more advanced stage at diagnosis were associated with increased mortality.
Conclusion. Vulvar cancer is common among elderly women with co-morbidities who present in advanced disease stage; all these factors are significant for survival.
With the discovery of the JAK2V617F mutation in patients with Philadelphia chromosome-negative (Ph-) myeloproliferative neoplasms (MPNs) in 2005, major advances have been made in the diagnosis of MPNs, in understanding of their pathogenesis involving the JAK/STAT pathway, and finally in the development of novel therapies targeting this pathway. Nevertheless, it remains unknown which mutations exist in approximately one-third of patients with non-mutated JAK2 or MPL essential thrombocythemia (ET) and primary myelofibrosis (PMF). At the end of 2013, two studies identified recurrent mutations in the gene encoding calreticulin (CALR) using whole-exome sequencing. These mutations were revealed in the majority of ET and PMF patients with non-mutated JAK2 or MPL but not in polycythemia vera patients. Somatic 52-bp deletions (type 1 mutations) and recurrent 5-bp insertions (type 2 mutations) in exon 9 of the CALR gene (the last exon encoding the C-terminal amino acids of the protein calreticulin) were detected and found always to generate frameshift mutations. All detected mutant calreticulin proteins shared a novel amino acid sequence at the C-terminal. Mutations in CALR are acquired early in the clonal history of the disease, and they cause activation of JAK/STAT signaling. The CALR mutations are the second most frequent mutations in Ph- MPN patients after the JAK2V617F mutation, and their detection has significantly improved the diagnostic approach for ET and PMF. The characteristics of the CALR mutations as well as their diagnostic, clinical, and pathogenesis implications are discussed in this review.
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.
The expanding impact of chronic kidney disease (CKD) due to pandemic diabetes mellitus is recounted emphasizing its epidemiology that has induced global socioeconomic stress on health care systems in industrialized nations now attempting to proffer optimal therapy for end stage renal disease (ESRD). Strategies to delay and perhaps prevent progression of diabetic nephropathy from minimal proteinuria through nephrotic range proteinuria and azotemia to ESRD appear to have decreased the rate of persons with diabetes who develop ESRD. For those with ESRD attributed to diabetes, kidney transplantation affords better survival and rehabilitation than either hemodialysis or peritoneal dialysis. It is likely that advances in genetics and molecular biology will suggest early interventions that will preempt diabetic complications including renal failure.
Parkinson’s disease (PD) and Alzheimer’s disease (AD) are severe neurodegenerative disorders, with no drugs that are currently approved to prevent the neuronal cell loss characteristic in brains of pa-tients suffering from PD and AD, and all drug treatments are symptomatic and monomodal in their action. Due to the complex pathophysiology, including a cascade of neurotoxic molecular events that result in neuronal death and predisposition to depression and eventual dementia, and etiology of these disorders, an innovative approach towards neuroprotection or neurorestoration (neurorescue) is the development and use of multifunctional pharmaceuticals which can act at different brain regions and neurons. Such drugs target an array of pathological pathways, each of which is believed to contribute to the cascades that ultimately lead to neuronal cell death. In this short review, we discuss examples of novel multifunctional ligands that may have potential as neuroprotective-neurorestorative therapeutics in PD and AD, some of which are under development. The compounds discussed originate from synthetic chemistry as well as from natural sources.
KEY WORDS: Rasagiline multimodal drugs, antiapoptotic, neuroprotection, neurorestoration, Parkinson’s disease, Alzheimer’s disease
Background—Bedside rounds have long been a time-honored component of medical education. Recently, there have been various recommendations that residency training programs further incorporate bedside teaching into clinical curricula.
Objectives—To compare these current attitudes regarding bedside education with the position of traditional Jewish law and ethics.
Methods—Relevant medical journal articles and traditional Jewish sources were reviewed.
Results—Halakha (the corpus of traditional Jewish law and ethics) gives greater focus to a patient-centered rather than student-centered bedside education experience.
Conclusion—Residency training programs should give greater consideration to the importance of a patient-centered bedside education experience.
Patient–physician interactions are increasingly influenced by the extraordinary diversification of populations and rapid expansion of medical knowledge that characterize our modern era. By contrast, the patient-physician interaction models currently used to teach medical trainees have little capacity to address these twin challenges. We developed a new model of patient-physician interaction to explicitly address these problems. Historically, models of patient–physician interaction viewed patient autonomy and the manifestation of clearly defined health care-related values as tightly linked, and it was assumed that patients’ medical knowledge was low. Unfortunately, this does not adequately represent patients such as 1) the highly educated non-medical specialist who possesses little familiarity with health-related values but is highly autonomous, and 2) the patient from a non-Western background who may have well-established health care-related values but a low sense of personal independence. In addition, it is evident to us that the assumption that all patients possess little medical knowledge can create alienation between patient and physician, e.g. the well-informed patient with a rare disease. We propose a para¬digm that models autonomy, health care-related values formation, and medical knowledge as varying from patient to patient. Four examples of patient types are described within the context of the model based on clinical experience. We believe that adopting this model will have implications for optimizing patient–physician interactions and teaching about patient-centered care. Further research is needed to identify relevant patient types within this framework and to assess the impact on health care outcomes.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic cardiac disorder characterized by life-threatening arrhythmias induced by physical or emotional stress, in the absence structural heart abnormalities. The arrhythmias may cause syncope or degenerate into cardiac arrest and sudden death which usually occurs during childhood. Recent studies have shown that CPVT is caused by mutations in the cardiac ryanodine receptor type 2 (RyR2) or calsequestrin 2 (CASQ2) genes. Both proteins are key contributors to the intracellular Ca2+ handling process, and play a pivotal role in Ca2+ release from the SR to the cytosol during systole. Although the molecular pathogenesis of CPVT is not entirely clear, it was suggested that the CPVT mutations promote excessive SR Ca2+ leak, which initiates delayed afterdepolarizations (DADs) and triggered arrhythmias in cardiac myocytes. The recent breakthrough discovery of induced pluripotent stem cells (iPSC) generated from somatic cells (e.g., fibroblasts, keratinocytes), now enables researches to investigate mutated cardiomyocytes generated from the patient's iPSC. To this end, in the present article we review recent studies on CPVT iPSC-derived cardiomyocytes, thus demonstrating in the mutated cells catecholamine-induced DADs and triggered arrhythmias.
We review three decades of unsuccessful efforts by public policy-makers in the United States to develop programs to lower the rate of preterm birth. We analyze why these efforts had been unsuccessful. Finally, we will speculate about whether something has changed in the last few years that might finally bend the curve and reverse the trend of a steadily rising preterm birth rate.
As more reports emerge of improved mortality and morbidity rates in infants born at the edge of viability, there may be need to reassess protocols and recommendations that encourage only comfort care for infants who are born at less than 24 weeks’ gestation. Analysis of those studies that report extremely poor survival of these infants reveals that, all too often, the results are measures of a self-fulfilling prophesy that reflects a predetermined non-aggressive global policy of no resuscitation and minimal investment in intensive care. Furthermore, little distinction is made between high- and low-risk infants of the same gestational age despite repeated studies that indicate that one can identify - subpopulations that have as much as a 20-50% increased chance of surviving with little if any long-term neurodevelopmental impairment. Thus, the need to reassess current policies is discussed.
