Onco-Hypertension: A Continuously Developing Field between Cancer and Hypertension.

The prognosis of cancer patients has greatly improved in the last years, owing to the development of novel chemotherapeutic agents. However, this progress comes with an increasing occurrence of cardiovascular adverse reactions. A serious side effect is arterial hypertension (HT), which is the most frequent comorbidity encountered in cancer patients, influencing the outcomes in cancer survivors. Even though secondary HT related to specific chemotherapeutic agents, such as vascular endothelial growth factor inhibitors, is usually mild and reversible, in rare instances it can be severe, leading to discontinuation of chemotherapy. In addition, HT per se has been studied as a potential risk factor for cancer development. The relationship is even more complex than previously thought, as concerning evidence recently highlighted the potential oncogenic effects of antihypertensive drugs, particularly thiazide diuretics, which may increase the risk of skin cancer. As a result, in light of the similar risk factors and overlapping pathophysiological mechanisms between HT and cancer, a promising concept of onco-hypertension has emerged, aiming to improve the understanding of the complicated interplay between these two pathologies and maintain a balance between the efficacy and risks of both antihypertensive drugs and chemotherapy agents.

Our experience of a paediatrician-led clinic for the medical management of children with obstructive sleep-disordered breathing.

BACKGROUND: Obstructive sleep-disordered breathing (OSDB) is very common in children. Adenotonsillectomy is usually curative, but there is emerging evidence that topical nasal steroids can also be effective for some children and may avoid the need for surgery. The number of children referred for assessment of OSDB is increasing and in some departments, waiting times are long. We established a paediatrician-led clinic for assessment and initial medical management of OSDB and in this study we report the proportion of children who avoided the need for surgery. METHOD: Referral letters to the otolaryngology department were screened and those with suspected OSDB and no significant co-morbidities were diverted to the paediatrician-led clinic. We recorded data for a consecutive series of children seen in this clinic with suspected OSDB over a 3-month period. Parents completed a 5-item subset of questions from the OSA-11 questionnaire before and after treatment with 6 weeks of topical nasal steroids. RESULTS: In the 3-month study period, 103 children were seen, with a mean age of 6 (range 1-16). Six (5.8%) had improved spontaneously before clinic attendance. Of the 97 children who were still symptomatic, 17 (17.5%) were referred directly for surgery on the basis of the severity of their symptoms, or because of other coexisting conditions that required surgical treatment (such as recurrent tonsillitis or otitis media). Three declined intranasal steroids. Seventy-seven had a trial of intranasal steroids, of whom 34 (35%) reported enough improvement to avoid surgery, and 29 (28%) failed to improve and were referred for surgery. Fourteen (14%) failed to attend after the trial of steroids: of these, 5 (5%) were contactable by phone and confirmed improvement after topical steroids. OSA-5 scores were significantly improved following intranasal steroids. DISCUSSION: A paediatrician-led clinic can be an effective way to ease the workload of an over-stretched otolaryngology service, and judicious use of topical nasal steroids can help around 40% of children with OSDB avoid surgery.

Petrified Ear - A Case Report and Review of the Literature.

Petrified ear is the transformation of normal, flexibleauricular cartilage into rigid, immobile auricularcartilage due to abnormal calcification or ossification.Etiologies of petrified ear include tissue injury,systemic endocrine diseases, congenital disorders,or petrified ear of unknown origin. We present a caseof a 69-year-old male with a one-month history ofnon-painful rigidity of the right ear that was found tohave petrified ear of unknown etiology confirmed byradiography.

Vascular complications in diabetes: Microparticles and microparticle associated microRNAs as active players.

The recognition of the importance of diabetes in vascular disease has greatly increased lately. Common risk factors for diabetes-related vascular disease include hyperglycemia, insulin resistance, dyslipidemia, inflammation, hypercoagulability, hypertension, and atherosclerosis. All of these factors contribute to the endothelial dysfunction which generates the diabetic complications, both macro and microvascular. Knowledge of diabetes-related vascular complications and of associated mechanisms it is becoming increasingly important for therapists. The discovery of microparticles (MPs) and their associated microRNAs (miRNAs) have opened new perspectives capturing the attention of basic and clinical scientists for their potential to become new therapeutic targets and clinical biomarkers. MPs known as submicron vesicles generated from membranes of apoptotic or activated cells into circulation have the ability to act as autocrine and paracrine effectors in cell-to-cell communication. They operate as biological vectors modulating the endothelial dysfunction, inflammation, coagulation, angiogenesis, thrombosis, subsequently contributing to the progression of macro and microvascular complications in diabetes. More recently, miRNAs have started to be actively investigated, leading to first exciting reports, which suggest their significant role in vascular physiology and disease. The contribution of MPs and also of their associated miRNAs to the development of vascular complications in diabetes was largely unexplored and undiscussed. In essence, with this review we bring light upon the understanding of impact diabetes has on vascular biology, and the significant role of MPs and MPs associated miRNAs as novel mediators, potential biomarkers and therapeutic targets in vascular complications in diabetes.

Stenotrophomonas maltophilia, a Pathogen of Increasing Relevance to Dermatologists: A Case Report and Review of the Literature.

Stenotrophomonas maltophilia is a Gram-negative bacillus that causes skin and soft tissue infections (SSTI), as well as bacteremia, pneumonia, and urinary tract infections. S. maltophilia infections are typically nosocomial and are often transmitted through water sources. Although historically described in immunocompromised hosts, S. maltophilia prevalence is increasing in both immunocompromised and immunocompetent populations. In light of high morbidity and mortality, it is critical that dermatologists are aware of this organism because of the limited options for therapy. Here, we describe a case of a S. maltophilia abscess with bacteremia in a patient with chronic lymphocytic leukemia and aplastic anemia that was successfully treated with trimethoprim-sulfamethoxazole. We also review the current standard of care and propose an algorithm for the treatment of S. maltophilia infection.

The Management of Hypertensive Emergencies-Is There a "Magical" Prescription for All?

Hypertensive emergencies (HE) represent high cardiovascular risk situations defined by a severe increase in blood pressure (BP) associated with acute, hypertension mediated organ damage (A-HMOD) to the heart, brain, retina, kidneys, and large arteries. Blood pressure values alone do not accurately predict the presence of HE; therefore, the search for A-HMOD should be the first step in the management of acute severe hypertension. A rapid therapeutic intervention is mandatory in order to limit and promote regression of end-organ damage, minimize the risk of complications, and improve patient outcomes. Drug therapy for HE, target BP, and the speed of BP decrease are all dictated by the type of A-HMOD, specific drug pharmacokinetics, adverse drug effects, and comorbidities. Therefore, a tailored approach is warranted. However, there is currently a lack of solid evidence for the appropriate treatment strategies for most HE. This article reviews current pharmacological strategies while providing a stepwise, evidence based approach for the management of HE.

Neutrophilic Dermatoses: a Clinical Update.

Purpose of Review: Neutrophilic dermatoses are defined by the presence of a sterile neutrophilic infiltrate on histopathology. This review focuses on the pathogenesis, epidemiology, clinicopathological features, diagnosis, and management of four disorders: Sweet syndrome, pyoderma gangrenosum, Behçet syndrome, and neutrophilic eccrine hidradenitis. Recent Findings: Recent studies have provided insight into the complex pathogenesis of neutrophilic dermatoses. Evidence supports an intricate interplay of abnormal neutrophil function and inflammasome activation, malignant transformation into dermal infiltrating neutrophils, and genetic predisposition. Summary: Neutrophilic dermatoses have diverse cutaneous and extracutaneous manifestations and may be associated with significant morbidity and mortality. Common underlying associations include infectious, inflammatory, and neoplastic disorders, as well as drug reactions. Emerging diagnostic and therapeutic frameworks identify an expanding role for biologic and targeted anti-inflammatory therapies.

Conditional Drug Approval as a Path to Market for Oncology Drugs in Canada: Challenges and Recommendations for Assessing Eligibility and Regulatory Responsiveness.

International drug regulators use conditional drug approval mechanisms to facilitate faster patient access to drugs based on a lower evidentiary standard typically required of drug approvals. Faster and earlier access is justified by limiting eligibility to drugs intended for serious and life-threatening diseases and by requiring post-market evidence collection to confirm clinical benefit. One such mechanism in Canada, the Notice of Compliance with Conditions (NOC/c) policy, was introduced in 1998. Today, most of the drugs approved under the NOC/c policy are for oncology indications. We analyze oncology drugs approvals under the NOC/c policy to inform discussions of two tradeoffs applied to conditional drug approvals, eligibility criteria and post-market evidence. Our analysis informs recommendations for Canada's proposed regulatory reforms approach to conditional approvals pathways. Our analysis demonstrates that under the current policy, eligibility criteria are insufficiently defined, resulting in their inconsistent application by Health Canada. Regulatory responsiveness to post-market evidence from post-market clinical trial and foreign jurisdiction regulatory decisions is slow and insufficient. In the absence of sufficient regulatory responsiveness, physicians and patients must make clinical decisions without the benefit of the best available evidence. Together, our analysis of the two core tradeoffs in Canada's conditional drug approval provides insight to inform the further development of Canada's proposed agile regulatory approach to drugs and devices that will expand the use of terms and conditions.

The Road to Better Management in Resistant Hypertension-Diagnostic and Therapeutic Insights.

Resistant hypertension (R-HTN) implies a higher mortality and morbidity compared to non-R-HTN due to increased cardiovascular risk and associated adverse outcomes-greater risk of developing chronic kidney disease, heart failure, stroke and myocardial infarction. R-HTN is considered when failing to lower blood pressure below 140/90 mmHg despite adequate lifestyle measures and optimal treatment with at least three medications, including a diuretic, and usually a blocker of the renin-angiotensin system and a calcium channel blocker, at maximally tolerated doses. Hereby, we discuss the diagnostic and therapeutic approach to a better management of R-HTN. Excluding pseudoresistance, secondary hypertension, white-coat hypertension and medication non-adherence is an important step when diagnosing R-HTN. Most recently different phenotypes associated to R-HTN have been described, specifically refractory and controlled R-HTN and masked uncontrolled hypertension. Optimizing the three-drug regimen, including the diuretic treatment, adding a mineralocorticoid receptor antagonist as the fourth drug, a ß-blocker as the fifth drug and an α1-blocker or a peripheral vasodilator as a final option when failing to achieve target blood pressure values are current recommendations regarding the correct management of R-HTN.

Deep neural networks for ECG-free cardiac phase and end-diastolic frame detection on coronary angiographies.

Invasive coronary angiography (ICA) is the gold standard in Coronary Artery Disease (CAD) imaging. Detection of the end-diastolic frame (EDF) and, in general, cardiac phase detection on each temporal frame of a coronary angiography acquisition is of significant importance for the anatomical and non-invasive functional assessment of CAD. This task is generally performed via manual frame selection or semi-automated selection based on simultaneously acquired ECG signals - thus introducing the requirement of simultaneous ECG recordings. In this paper, we evaluate the performance of a purely image based workflow relying on deep neural networks for fully automated cardiac phase and EDF detection on coronary angiographies. A first deep neural network (DNN), trained to detect coronary arteries, is employed to preselect a subset of frames in which coronary arteries are well visible. A second DNN predicts cardiac phase labels for each frame. Only in the training and evaluation phases for the second DNN, ECG signals are used to provide ground truth labels for each angiographic frame. The networks were trained on 56,655 coronary angiographies from 6820 patients and evaluated on 20,780 coronary angiographies from 6261 patients. No exclusion criteria related to patient state (stable or acute CAD), previous interventions (PCI or CABG), or pathology were formulated. Cardiac phase detection had an accuracy of 98.8 %, a sensitivity of 99.3 % and a specificity of 97.6 % on the evaluation set. EDF prediction had a precision of 98.4 % and a recall of 97.9 %. Several sub-group analyses were performed, indicating that the cardiac phase detection performance is largely independent from acquisition angles, the heart rate of the patient, and the angiographic view (LCA / RCA). The average execution time of cardiac phase detection for one angiographic series was on average less than five seconds on a standard workstation. We conclude that the proposed image based workflow potentially obviates the need for manual frame selection and ECG acquisition, representing a relevant step towards automated CAD assessment.

Side-by-side Comparison of a Picosecond 755-nm Alexandrite Laser and a Quality-switched 1064-nm Neodymium-doped Yttrium Aluminum Garnet Laser in the Treatment of Argyria.

Argyria is a rare but cosmetically distressing and difficult-to-treat condition for which quality-switched (Q-switched) lasers have been most commonly employed. However, at least one previous report suggests that the picosecond alexandrite laser may also serve as a successful treatment modality. Herein, we present a side-by-side comparison of a picosecond 755-nm alexandrite laser and a Q-switched 1064-nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser in the treatment of argyria. Our results reveal an equivalent success of the picosecond alexandrite when compared to the more commonly employed Q-switched Nd:YAG, suggesting that the picosecond 755-nm alexandrite laser is equally effective in the treatment of argyria.

The Romanian Society of Internal Medicine's Choosing Wisely Campaign.

Quality of care in medicine is not necessarily proportional to quantity of care and excess is often useless or even more, potentially detrimental to our patients. Adhering to the European Federation of Internal Medicine's initiative, the Romanian Society of Internal Medicine (SRMI) launched the Choosing Wisely in Internal Medicine Campaign, aiming to cut down diagnostic procedures or therapeutics overused in our country. A Working Group was formed and from 200 published recommendations from previous international campaigns, 36 were voted as most important. These were submitted for voting to the members of the SRMI and posted on a social media platform. After the two voting rounds, the top six recommendations were established. These were: 1. Stop medicines when no further benefit is achieved or the potential harms outweigh the potential benefits for the individual patient. 2. Don't use antibiotics in patients with recent C. difficile without convincing evidence of need. 3. Don't regularly prescribe bed rest and inactivity following injury and/or illness unless there is scientific evidence that harm will result from activity. Promote early mobilization. 4. Don't initiate an antibiotic without an identified indication and a predetermined length of treatment or review date. 5. Don't prescribe opioids for treatment of chronic or acute pain for sensitive jobs such as operating motor vehicles, forklifts, cranes or other heavy equipment. 6. Transfuse red cells for anemia only if the hemoglobin concentration is less than 7 g/dL or if the patient is hemodynamically unstable or has significant cardiovascular or respiratory comorbidity. Don't transfuse more units of blood than absolutely necessary.

Cardiovascular risk factors in a Roma sample population from Romania.

BACKGROUND: The Roma population has a high prevalence of cardiovascular risk factors, higher mortality, and shorter life expectancy. It is found in the largest number in Romania, but published data are still scarce here. We studied cardiovascular risk factors and disease along with target organ damage on a population of Roma inhabitants from Bucharest, Romania. METHODS: This cross-sectional study enrolled 806 Roma subjects (18-83 years), in a community-based participatory research manner. Demographics included anthropometric data, a questionnaire on social status, education, medical history, and health deleterious behaviors. Medical evaluation included clinical examination, blood pressure, ankle-brachial index, pulse wave velocity measurements, blood tests (complete blood count, lipid profile, glucose, creatinine, uric acid), dip-stick microalbuminuria, dilated fundoscopy, ECG, and echocardiography. RESULTS: Prevalence of all cardiovascular risk factors was high, peaking in abnormal lipid metabolism (82.13%), heavy smoking (63.02% including ex-smokers) and obesity (50.99%). The first and the latter were actually similar to the general population in Romania. Almost half of subjects were at high or very high risk for fatal cardiovascular disease. CONCLUSIONS: The study shows that the Roma population in a more affluent region in Romania shares a similarly high cardiovascular burden to their surrounding community.

Target Organ Damage and Cardiovascular Risk in a Hypertensive Roma Sample Population in Romania.

BACKGROUND: The largest European Roma community resides in Romania, but there is still little published data on cardiovascular (CV) risk factors and disease in this group. This study addresses the prevalence of arterial hypertension, associated CV disease risk, and target organ damage (TOD) in a Roma community from Bucharest, Romania. METHODS: This is a cross-sectional community-based participatory research to assess for CV risk factors, TOD and CV disease, including 806 Roma ethnics (18-83 years) integrated in the local community, 36.16% males. Evaluation included physical examination with blood pressure, pulse wave velocity and anklebrachial measurements, laboratory tests, ECG, echocardiography and fundoscopy. RESULTS: Prevalence of hypertension was 33.62%, awareness 76.38%, higher in females (p>0.01), and control rate 44.39%. Compared to age-matched normotensives, hypertensives had more left ventricle hypertrophy and more frequently increased pulse pressure. Differences in TOD were attenuated between newly and previously diagnosed, controlled and uncontrolled, hypertensives. Cardiovascular disease was almost absent in normotensives. Ten-year risk for fatal CV disease followed an increasing trend from normotension to long standing hypertension. CONCLUSION: This is the first dedicated study to thoroughly assess TOD and risk for fatal CV disease in a Romanian Roma population. Hypertension was less prevalent than in the general population, with similar awareness, possibly as a consequence of integration in the surrounding community. Fatal CV disease risk followed the trend of increasing prevalence of risk factors, and hypertension played an important role in its modulation.

Diet and rosacea: the role of dietary change in the management of rosacea.

Dietary change may play a role in the therapy of rosacea. Certain foods and beverages may act as "triggers" for rosacea exacerbations. These may be divided into heat-related, alcohol-related, capsaicin-related, and cinnamaldehyde-related. One potential pathogenic mechanism may be via the activation of transient receptor potential cation channels, which result in neurogenic vasodilatation. Further research is needed on the role of the gut skin connection in rosacea. Epidemiologic studies suggest that patients with rosacea have a higher prevalence of gastrointestinal disease, and one study reported improvement in rosacea following successful treatment of small intestinal bacterial overgrowth. While further research is required in this area, patients may be advised on measures to support a healthy gut microbiome, including the consumption of a fiber-rich (prebiotic) diet.

Backbone 1H, 13C, and 15N NMR resonance assignments of the Krüppel-like factor 4 activation domain.

Krüppel-like factor 4 (KLF4) is a transcription factor involved in diverse biological processes, including development, cellular differentiation and proliferation, and maintenance of tissue homeostasis. KLF4 has also been associated with disease states, such as cardiovascular disease and several cancers. KLF4 contains an activation domain, repression domain, and a structurally characterized C-terminal zinc finger domain that mediates its binding to DNA. The structurally uncharacterized KLF4 activation domain is critical for transactivation by KLF4 and mediates its binding to the transcriptional coactivator CBP/p300. Here, we report the 1H, 15N, 13CO, 13Cα and 13Cß NMR chemical shift assignments of KLF41-130, which contains the KLF4 activation domain. Narrow chemical shift dispersion in the 1H dimension of the 1H-15N HSQC spectrum suggests that the KLF41-130 fragment is intrinsically disordered.