Urological malignancies are a major source of morbidity and mortality in men over 40. Screening for those malignancies has a potential benefit of reducing both. However, even after more than two decades of screening for prostate cancer, the implications of most resulting information are still a matter of debate. Controversy extends over several aspects of prostate cancer screening programs, including age of onset, defining populations at risk, most appropriate intervals, as well as the optimal methods to be used for screening. The medical community is still divided regarding the effectiveness of prostate cancer-related death prevention and its benefits-to-harms ratio, reflecting an inconsistency regarding screening recommendations. Similarly, benefits of screening for urothelial and kidney tumors are yet lacking high- level evidence, although recent evidence supports screening of populations at risk. Clearly, the current era of evolving molecular and genetic biomarkers harbors the potential to change screening practice. In this paper, we review current guidelines as well as giving an update on new developments which might influence screening strategies in common urological malignancies.
An ideological case study based on medical profession norms during the Third Reich will be used to exemplify the importance of diversity in the manifestations of professional ethics. The German professional medical community banned their Jewish colleagues from treating German citizens. This included legally mandated employment discrimination and outright censure which led to a professional ethic devoid of diverse voices. While the escalation to the T-4 program and medicalized genocide was influenced by many causes, the intentional, ethnocentric-based exclusion of voices was an important contributing element to the chronicled degradation of societal mores. For illustration, six core Jewish values—life, peace, justice, mercy, scholarship, and sincerity of intention—will be detailed for their potential to inspire health-care professionals to defend and protect minorities and for readers to think critically about the role of medical professionalism in Third Reich society. The Jewish teachings highlight the inherent professional obligations physicians have toward their patients in contrast to the Third Reich’s corruption of patient-centered professionalism. More fundamentally, juxtaposing Jewish and Nazi teachings exposes the loss of perspective when a profession’s identity spurns diversity. To ensure respect for persons in all vulnerable minorities, the first step is addressing professional inclusion of minority voices.
Objectives: Peripartum cardiomyopathy (PPCM) is a serious complication of pregnancy. Studies investigating the risk factors that worsen outcomes have yielded conflicting results. The goals of this study were to describe the clinical and echocardiographic characteristics of PPCM in a single tertiary center and to determine the prognostic factors associated with persistence of left ventricular (LV) dysfunction in these women.
Study Design: This retrospective cross-sectional population-based cohort study included all patients with PPCM confirmed by echocardiography who delivered at our center from 2004 to 2014. Two groups were compared to determine long-term maternal outcome: (1) those who recovered normal LV function; and (2) those with residual systolic LV dysfunction.
Results: There were 148,994 deliveries during the study period. Of these, 89,196 patients were Bedouin and 59,798 were non-Bedouin. Forty-six patients met the PPCM study inclusion criteria. The PPCM prevalence for the total deliveries was 1:3,239. The PPCM prevalence among Bedouin patients was 1:2,787 versus non-Bedouin patients of 1:4,983 (P=0.037). None of the women had pre-existing chronic hypertension, and there was no maternal death. Patients who had severe or moderate LV dysfunction at the clinical presentation of PPCM were less likely to regain normal LV function than those with mild dysfunction (81.2% versus 56.7%, P=0.009). Based on initial echocardiogram, a trend toward residual LV dysfunction was noted in patients with a dilated left ventricle as compared to those with a non-dilated left ventricle (18.8% versus 6.7%, P=0.32). A hypokinetic right ventricle was found in 15.2% of the women who suffered from PPCM.
Conclusion: In our cohort, Bedouin women may be at increased risk for PPCM, and patients with severe LV dysfunction have a lower chance of recovery from PPCM.
The porphyrias are a group of rare metabolic disorders, inherited or acquired, along the heme biosynthetic pathway, which could manifest with neurovisceral and/or cutaneous symptoms, depending on the defective enzyme. Neurovisceral porphyrias are characterized by acute attacks, in which excessive heme production is induced following exposure to a trigger. An acute attack usually presents with severe abdominal pain, vomiting, and tachycardia. Other symptoms which could appear include hypertension, hyponatremia, peripheral neuropathy, and mild mental symptoms. In severe attacks there could be severe symptoms including seizures and psychosis. If untreated, the attack might become very severe, affecting the peripheral, central, and autonomic nervous system, leading to paralysis, respiratory failure, hyponatremia, coma, and even death. From the biochemical point of view, acute attacks are involved with increased levels of precursors in the heme biosynthetic pathway, up to the deficient step. Of these precursors, aminolevulinic acid (ALA) is considered to be neurotoxic. Treatment is directed to reduce ALA production by reducing the activity of the enzyme aminolevulinate synthase (ALAS)—most effectively by heme therapy. Cutaneous symptoms are a consequence of elevated porphyrins in the blood stream. These porphyrins react to light; therefore sun-exposed areas are affected, producing fragile erosive skin lesions in porphyria cutanea tarda (PCT) or non-scarring stinging and burning symptoms in erythropoietic protoporphyria (EPP). Unlike the most common neurovisceral porphyria, acute intermittent porphyria (AIP), variegate porphyria (VP), and hereditary coproporphyria (HCP) can have cutaneous symptoms as well. Differentiating them from other cutaneous porphyrias is essential for accurate diagnosis, treatment, and patient recommendations.
Chemotherapy-associated myocardial toxicity is increasingly recognized with the expanding armamentari¬um of novel chemotherapeutic agents. The onset of cardiotoxicity during cancer therapy represents a major concern and often involves clinical uncertainties and complex therapeutic decisions, reflecting a compro¬mise between potential benefits and harm. Furthermore, the improved cancer survival has led to cardio¬vascular complications becoming clinically relevant, potentially contributing to premature morbidity and mortality among cancer survivors. Specific higher-risk populations of cancer patients can benefit from pre¬vention and screening measures during the course of cancer therapies. The pathobiology of chemotherapy-induced myocardial dysfunction is complex, and the individual patient risk for heart failure entails a multifactorial interaction between the selected chemotherapeutic regimen, traditional cardiovascular risk factors, and individual susceptibility. Treatment with several specific chemotherapeutic agents, including anthracyclines, proteasome inhibitors, epidermal growth factor receptor inhibitors, vascular endothelial growth factor inhibitors, and immune checkpoint inhibitors imparts increased risk for cardiotoxicity that results from specific therapy-related mechanisms. We review the pathophysiology, risk factors, and imaging considerations as well as patient surveillance, prevention, and treatment approaches to mitigate cardiotox¬icity prior, during, and after chemotherapy. The complexity of decision-making in these patients requires viable discussion and partnership between cardiologists and oncologists aiming together to eradicate cancer while preventing cardiotoxic sequelae.
Objective: The aim of the present study was to determine and compare the expression pattern and localization of nestin, in an attempt to explore its role in oral carcinogenesis.
Methods: Western blot and immunohistochemistry analysis were performed to study the expression pattern of nestin in normal mucosa, leukoplakia, and oral squamous cell carcinoma samples. Nestin expres¬sion was evaluated in the keratinocytes and blood vessels of all the samples and compared with various clinico-pathological parameters.
Results: Nestin expression was increased in samples of leukoplakia and oral squamous cell carcinoma when compared with normal mucosa. Among leukoplakia samples, the expression was increased in cases without dysplasia compared to cases with dysplastic features. In cases of oral squamous cell carcinoma, the expression of nestin was found to be decreased with the loss of differentiation. Neoangiogenesis status determined by nestin expression showed an increasing expression from normal mucosa through leuko-plakia, to oral squamous cell carcinoma.
Conclusion: This study has two major findings: 1) identification of nestin as an effective indicator of neo-angiogenesis, and 2) nestin may be used as a marker in predicting the early changes in oral carcinogenesis.
Good morning. It is a great pleasure to share my thoughts with you here in Israel. The last day I was here was June 25, 2016, which was the day of the results of the Brexit referendum. My wife and I escaped feeling so depressed, but at least, we thought, we are leaving this behind; but when we came to Israel the only thing people wanted to talk about was the Brexit referendum!
Here I am today, on October 31, 2019, the day that we were meant to be leaving the European Union, so there is something with my connection with Israel and Brexit that I don’t understand! Let me start by saying that we have the privilege of being participants in a biomedical and health science revolution. I don’t think that is overstating it. We are living in an extraordinary, exciting time. Let me remind you of some of these fields that are moving so fast.
Anti-citrullinated protein antibodies (ACPAs) are highly specific serologic markers for rheumatoid arthritis (RA) and can pre-date clinical disease onset by up to 10 years, also predicting erosive disease. The process of citrullination, the post-translational conversion of arginine to citrulline residues, is mediated by peptidylarginine deiminase (PAD) enzymes present in polymorphonuclear cells (PMNs). Calcium ions (Ca2+) are required for PAD activation, but the intracellular Ca2+ concentration in normal cells is much lower than the optimal Ca2+ concentration needed for PAD activation. For this reason, it has been proposed that PAD activation, and thus citrullination, occurs only during PMN cell death when PAD enzymes leak out of the cells into the extracellular matrix, or extracellular Ca2+ enters the cells, with the high Ca2+ concentration activating PAD. Recently, using artificial in vitro systems to corroborate their hypothesis, Romero et al. demonstrated that “hypercitrullination,” citrullination of multiple intracellular proteins, occurs within synovial fluid (SF) cells of RA patients, and that only modes of death leading to membranolysis such as perforin-granzyme pathway or complement membrane attack complex activation cause hypercitrullination. In order for Romero’s hypothesis to hold, it is reasonable to surmise that PMN-directed lysis should occur in the rheumatoid joint or the circulation of RA patients. Research conducted thus far has shown that immunoglobulin G (IgG) targeting PMNs are present in RA SF and mediate PMN activation. However, the role of anti-PMN IgG in mediating complement activation and subsequent PMN lysis and hypercitrullination has not been fully evaluated.
Background: The PROSPECT (Procedure-Specific Postoperative Pain Management) Group recommended a single injection femoral nerve block in 2008 as a guideline for analgesia after total knee arthroplasty. Other authors have recommended the addition of sciatic and obturator nerve blocks. The lateral femoral cutaneous nerve is also involved in pain syndrome following total knee arthroplasty. We hypothesized that preoperative blocking of all four nerves would offer superior analgesia to femoral nerve block alone.
Methods: This is a prospective, randomized, controlled, and observer-blinded clinical study. A total of 107 patients were randomly assigned to one of three groups: a femoral nerve block group, a multiple nerve block group, and a control group. All patients were treated postoperatively using patient-controlled intravenous analgesia with morphine. Pain intensity at rest, during flexion and extension, and morphine consumption were compared between groups over three days.
Results: A total of 90 patients completed the study protocol. Patients who received multiple nerve blocks experienced superior analgesia and had reduced morphine consumption during the postoperative period compared to the other two groups. Pain intensity during flexion was significantly lower in the “blocks” groups versus the control group. Morphine consumption was significantly higher in the control group.
Conclusions: Pain relief after total knee arthroplasty immediately after surgery and on the first postoperative day was significantly superior in patients who received multiple blocks preoperatively, with morphine consumption significantly lower during this period. A preoperative femoral nerve block alone produced partial and insufficient analgesia immediately after surgery and on the first postoperative day. (Clinical trial registration number (NIH): NCT01303120)
Osteoporosis is a common condition with significant health care costs. First-line therapy is with bisphosphonates, which have proven anti-fracture efficacy. Around 10 years after the introduction of bisphosphonates reports began to be published of atypical femoral fractures (AFFs) that may be associated with this therapy. These fractures are associated with significant morbidity although lower mortality than the more common osteoporotic neck-of-femur fractures. A case definition has been described to allow identification of this class of fracture. Further work has established a high relative risk of AFFs in patients treated with bisphosphonates, but a low absolute risk in comparison to that of osteoporotic fractures. Proposed pathological mechanisms include low bone turnover states leading to stress/insufficiency fractures. Clinicians should be aware of the risk of AFFs and in particular the high rate of prodromal thigh/groin pain that warrants investigation in a patient receiving a bisphosphonate. If an incomplete fracture is diagnosed then bisphosphonate therapy needs to be stopped and prophylactic surgery may be considered. Due to these rare side effects patients on bisphosphonates require regular review, and this is particularly advised after 5 years of oral or 3 years of intravenous therapy.
