Expert proposal to analyze the combination of aortic and mitral regurgitation in multiple valvular heart disease by comprehensive echocardiography.

The assessment of valvular pathologies in multiple valvular heart disease by echocardiography remains challenging. Data on echocardiographic assessment-especially in patients with combined aortic and mitral regurgitation-are rare in the literature. The proposed integrative approach using semi-quantitative parameters to grade the severity of regurgitation often yields inconsistent findings and results in misinterpretation. Therefore, this proposal aims to focus on a practical systematic echocardiographic analysis to understand the pathophysiology and hemodynamics in patients with combined aortic and mitral regurgitation. The quantitative approach of grading the regurgitant severity of each compound might be helpful in elucidating the scenario in combined aortic and mitral regurgitation. To this end, both the individual regurgitant fraction of each valve and the total regurgitant fraction of both valves must be determined. This work also outlines the methodological issues and limitations of the quantitative approach by echocardiography. Finally, we present a proposal that enables verifiable assessment of regurgitant fractions. The overall interpretation of echocardiographic results includes the symptomatology of patients with combined aortic and mitral regurgitation and the individual treatment options with respect to their individual risk. In summary, a reproducible, verifiable, and transparent in-depth echocardiographic investigation might ensure consistent hemodynamic plausibility of the quantitative results in patients with combined aortic and mitral regurgitation.

Expert proposal to characterize cardiac diseases with normal or preserved left ventricular ejection fraction and symptoms of heart failure by comprehensive echocardiography.

Currently, the term "heart failure with preserved left ventricular ejection fraction (HFpEF)" is based on echocardiographic parameters and clinical symptoms combined with elevated or normal levels of natriuretic peptides. Thus, "HFpEF" as a diagnosis subsumes multiple pathophysiological entities making a uniform management plan for "HFpEF" impossible. Therefore, a more specific characterization of the underlying cardiac pathologies in patients with preserved ejection fraction and symptoms of heart failure is mandatory. The present proposal seeks to offer practical support by a standardized echocardiographic workflow to characterize specific diagnostic entities associated with "HFpEF". It focuses on morphological and functional cardiac phenotypes characterized by echocardiography in patients with normal or preserved left ventricular ejection fraction (LVEF). The proposal discusses methodological issues to clarify why and when echocardiography is helpful to improve the diagnosis. Thus, the proposal addresses a systematic echocardiographic approach using a feasible algorithm with weighting criteria for interpretation of echocardiographic parameters related to patients with preserved ejection fraction and symptoms of heart failure. The authors consciously do not use the diagnosis "HFpEF" to avoid misunderstandings. Central illustration: Scheme illustrating the characteristic echocardiographic phenotypes and their combinations in patients with "HFpEF" symptoms with respect to the respective cardiac pathology and pathophysiology as well as the underlying typical disease.

[Valvular heart disease in patients with chronic kidney disease]. / Herzklappenvitien bei chronischer Niereninsuffizienz.

Valvular heart disease is a common comorbidity in patients with impaired renal function, especially in those with end-stage renal disease undergoing dialysis. Sclerosis and calcification of the heart valves and the valve ring are particularly relevant in the etiology of the diseases. These typically occur at the aortic and mitral valves and can lead to both insufficiency and stenosis of the affected valve. In the current guidelines of the European Society for Cardiology published in 2017, surgical treatment remains the standard of care for most forms of severe valvular heart disease; however, the presence of chronic kidney disease impairs clinical outcomes and is associated with higher mortality rates when compared to patients with preserved renal function. Catheter-based treatment options have emerged as an effective and safe alternative for patients >75 years and/or with increased surgical risk. Consequently, in patients with appropriate anatomy and elevated risk, interventional treatment options should also be discussed in the heart team.

[Cardiovascular pharmacotherapy and coronary revascularization in end-stage renal failure]. / Kardiovaskuläre Pharmakotherapie und koronare Revaskularisation bei terminaler Niereninsuffizienz.

There is a close physiological relationship between the kidneys and the heart. Cardiovascular diseases are the most prevalent cause of death in patients with chronic kidney disease (CKD), whereas CKD may directly accelerate the progression of cardiovascular diseases and is considered to be a cardiovascular risk factor. In patients with mild CKD, i.e. an estimated glomerular filtration rate (eGFR) >60 ml/min/1.73 m2, treatment of coronary artery disease and chronic heart failure is not essentially different from patients with preserved renal function; however, as most pivotal trials have systematically excluded patients with advanced renal failure, many treatment recommendations in this patient group are based on observational studies, post hoc subgroup analyses and meta-analyses or pathophysiological considerations, which are not supported by controlled studies. Therefore, prospective randomized studies on the management of heart failure and coronary artery disease are needed, which should specifically focus on the growing number of patients with advanced renal functional impairment.

Do patients with diabetes type 2 or chronic heart failure understand a medication plan?

A standardized medication plan (MP) was recently enacted into German law (§ 31a SGB V). The purpose of our study was to assess if patients with chronic diseases requiring polymedication understand the standardized MP and can transfer the given information into practice. 100 patients who took at least five medicines regularly were prospectively included in a cross-sectional study: 50 patients with the primary diagnosis chronic heart failure (CHF), and 50 with diabetes mellitus type 2 (DMT2). We performed a structured test-scenario studying the handling of a provided MP then evaluated the execution of the information on the MP by filling pill boxes and requested patients' opinion. An established weighted scoring system, the "Evaluation Tool to test the handling of the Medication Plan" (ET-MP) was applied to quantitate the ability of the patients to handle the MP. In addition, signs of depression, cognitive function and self-care behavior in chronic heart failure were characterized using the PHQ-9, Mini-Cog, and G9-EHFScB-9 questionnaires, respectively. The understanding of the MP was poor and irrespective of the underlying primary diagnosis. Only 32% of all patients were able to handle the MP without difficulties (ET-MP score >90%), the median ET-MP score was 83 [(IQR) 50-98]. Comprehension of the MP was better in patients aged <70 years compared to ≥70 years (p<0.01). Patients ≥10 years of education achieved higher ET-MP results than patients with <10 years of education (p<0.01). Patients with signs of cognitive impairment exhibited significantly lower ET-MP scores than patients without cognitive impairment (p<0.001). There were no significant correlations of the ET-MP score with number of daily medications, living situation, sex, the Charlson Comorbidity Index, the PHQ-9 score, and use of a dosing aid or possession of a medication list.

[Chronic heart failure : current guideline recommendations and innovations]. / Chronische Herzinsuffizienz : Aktuelle Leitlinienempfehlungen und neue Erkenntnisse.

Chronic heart failure is one of the most common chronic diseases worldwide with increasing prevalence and incidence. Due to the high morbidity and mortality a standardized and evidence-based therapy is essential. The present article gives an overview of the innovations from 2014 based on the current guidelines of the European Society of Cardiology. First, improvements of established medication regimens regarding beta blockers, mineralocorticoid receptor antagonists and treatment options for heart rate reduction and disease management programs will be explained. Second, new pharmacological developments, such as the new substance class of angiotensin receptor blockers and neprilysin inhibitors (ARNI), will be presented. Finally, new insights into common comorbidities of chronic heart failure patients, such as atrial fibrillation and hyperkalemia will be discussed.

Homelessness and housing crises among individuals accessing services within a Canadian emergency department.

ACCESSIBLE SUMMARY: Studies have indicated that individuals who are homeless access hospital emergency departments more frequently and may have different needs than individuals who are housed. Successful interventions have been developed and tested to reduce discharge to homelessness for psychiatric inpatients but have not been similarly tested for discharge from emergency departments. This study was developed to provide baseline data on this issue to inform future emergency department interventions. Findings from the current study suggest that discharge from emergency departments to homelessness happens frequently in London, Canada. Participants are unlikely to spontaneously disclose their housing/homelessness issue when first entering the emergency department, which may result in services that do not adequately meet their complex needs. Screening for housing issues is necessary within emergency departments and psychiatric crisis teams as housing issues may be a reason for accessing care or contribute to the presenting condition. Nurses are in an ideal position to evaluate housing needs among emergency department patients. Services outside of the emergency department are also needed to address housing issues, particularly outside of regular office hours. ABSTRACT: Individuals who have mental health issues and are homeless or in housing crisis have been found to access emergency departments more frequently than individuals with stable housing. While emergency departments primarily focus on medical issues, homeless individuals may require psychosocial support as well. This study examined issues around housing crises and emergency department use for individuals with mental illness in Canada. Collecting baseline data about these issues is important to inform subsequent interventions. Administrative data from a hospital emergency department and psychiatric crisis service were collected, and five individuals accessing the emergency department for psychiatric reasons were interviewed. Results indicated that individuals with an identified housing crisis accessed the emergency department 930 times in 6 months. None of the interview participants identified housing as the primary reason for accessing the emergency department, but all noted that housing was a contributing stressor. Future research is needed to examine ways in which discharge to homelessness from emergency departments can be avoided and identify alternative services to address housing concerns, particularly for individuals with mental illness. Crisis service and emergency department staff, especially nurses, can play an important role in screening for housing issues and connecting individuals to outside services.

When a patient's ethnicity is declared, medical students' decision-making processes are affected.

BACKGROUND: Disparity in health status and healthcare outcomes is widespread and well known. This holds true for Indigenous peoples in many settings including Australia and Hawaii. While multi-factorial, there is increasing evidence of health practitioner contribution to this disparity. This research explored senior medical students' clinical decision-making processes. METHODS: A qualitative study was conducted in 2014 with 30 final year medical students from The University of Melbourne, Australia, and The John Burns Medical School, Hawaii, USA. Each student responded to questions about a paper-based case, first in writing and elaborated further in an interview. Half the students were given a case of a patient whose ethnicity was not declared; the other half considered the patient who was Native Hawaiian or Australian Aboriginal. A systematic thematic analysis of the interview transcripts was conducted. RESULTS: The study detected subtle biases in students' ways of talking about the Indigenous person and their anticipation of interacting with her as a patient. Four main themes emerged from the interview transcripts: the patient as a person; constructions of the person as patient; patient-student/doctor interactions; and the value of various education settings. There was a strong commitment to the patient's agenda and to the element of trust in the doctor-patient interaction. CONCLUSION: These findings will help to advance medical curricula so that institutions graduate physicians who are increasingly able to contribute to equitable outcomes for all patients in their care. The study also draws attention to subtle biases based on ethnicity that may be currently at play in physicians' practices.

[Interventional hypertension therapy in diabetes mellitus. Effects on blood pressure and glucose metabolism?]. / Interventionelle Hypertonietherapie bei Diabetes mellitus. Effekte auf Blutdruck und Glukosestoffwechsel?

Hypertension is the most common chronic cardiovascular disease with increasing prevalence all over the world. Despite the availability of many effective antihypertensive drugs, blood pressure control to target values remains low. In the pathophysiology of therapy resistant hypertension, increased activity of the sympathetic nervous system with an imbalance between sympathetic and parasympathetic activity has been identified as a main contributor to the development and maintenance of hypertension. Catheter-based denervation of the renal sympathetic nerves has been described as reducing blood pressure and decreasing sympathetic activity in patients with resistant hypertension. Supplementary beneficial effects on common cardiovascular comorbidities, such as diabetes type 2, have been reported. The present review aims to give an overview about percutaneous renal denervation for treatment of hypertension and potential new therapeutic options to improve glycemic control.

Visual adaptation to interocular brightness differences induced by neutral-density filters.

PURPOSE: Interocular brightness differences such as those caused by asymmetrical cataract have been found to have a minimal effect on interocular brightness matches. In the present study, the measured binocular visual response to interocular differences in retinal illuminance was measured over time. METHODS: Interocular differences in retinal illuminance of magnitudes 0.3, 0.6, and 0.9 log units were induced using neutral density (ND) filters under two conditions: (1) naturally mobile pupils and (2) with fixed artificial pupils (3 mm). Interocular brightness differences were quantified by measuring interocular brightness matches using the simultaneous interocular brightness sense test every 15 minutes over a 2-hour period in eight visually normal subjects. RESULTS: Initial interocular brightness matches were as predicted by the induced interocular differences in retinal illuminance (P > 0.05). A significant reduction in the interocular difference in brightness was observed over time (P < 0.01). These reductions in the interocular difference in brightness over time followed a logarithmic progression reaching asymptotic values equal to the reciprocal of the square root of the interocular retinal illuminance ratio. This value is equal to the midpoint of the induced interocular difference in retinal illuminance at time 0 and that found without the introduction of the ND filters. Binocular visual adaptation to interocular brightness differences occurred with both mobile and fixed pupils. CONCLUSIONS: Visual adaptation occurs in response to interocular brightness differences induced by asymmetrical ND filters. The level of visual adaptation can be predicted by Fechner's Paradox and is independent of interocular differences in pupil diameter.

Suppression of growth of tumour cell lines in vitro and tumours in vivo by mistletoe lectins.

A variety of studies have shown that incubation of different tumour cell lines with mistletoe lectins (MLs) in vitro has a marked cytotoxic effect. In the concentration range of low cytotoxicity cell death induced by ML-I is quantitatively due to apoptotic processes. The first events observed being membrane perforation and protusions. Simultaneous treatment of certain tumour cells with MLs rendered them more sensitive to induction of apoptosis by TNFalpha. The immunomodulatory activity of ML-I was investigated by measuring cytokine release and the results confirmed that cytokine induction by the lectin is regulated at the transcriptional level. ML-I has been shown to potentiate the effect of chemotherapeutic drugs. In addition to an in vitro effect a number of workers have demonstrated that MLs suppress tumour growth in vivo. Mistletoe lectins have been administered to animals locally to the tumour, systemic, subcutaneously or by the oral route via the diet. In many cases apoptosis was observed in the tumour and instances where complete tumour ablation has occurred have been reported. It has been hypothesized that the anticancer efficacy of tumour necrosis factor-alpha (TNFalpha) is potentiated by MLs isolated from both European and Korean mistletoe. There is accumulating evidence that both types of MLs are able to induce an anti-angiogenic response in the host suggesting that the anti-metastatic effect observed on a series of tumour cell lines in mice is in part due to an inhibition of tumour-induced angiogenesis and in part due to an induction of apoptosis.

A comparison of the effect of two anaesthetic techniques on surgical conditions during gynaecological laparoscopy.

In a prospective, randomised, controlled trial, we compared the effects of two anaesthetic techniques on surgical conditions during day-case, gynaecological laparoscopic procedures in 40 female patients. Patients were allocated randomly to two groups, either to breathe spontaneously through a laryngeal mask airway or to receive a neuromuscular-blocking agent (NMB) and have the lungs ventilated via a tracheal tube. We then measured the number of attempts of Verres' needle insertion, initial intra-abdominal pressure, time to reach a steady 15 mmHg (1.97 kPa) of intra-abdominal pressure, adequacy of the pneumoperitoneum, operative view and duration of operation. We found that the initial intra-abdominal pressure was higher and the operation time shorter in the laryngeal mask group. The adequacy of the pneumoperitoneum for trocar placement was better in the NMB group. We conclude that the anaesthetic technique of spontaneously breathing through a laryngeal mask airway reduces total operation time. However surgeons should be aware of the different abdominal pressure patterns produced by each anaesthetic technique, and anaesthetists must consider the implications of the anaesthetic technique on surgical safety.

Dietary mistletoe lectin supplementation and reduced growth of a murine non-Hodgkin lymphoma.

The growth of a murine non-Hodgkin lymphoma (NHL) tumour has been shown to be reduced by incorporating mistletoe lectin (ML-1) into the diet. The morphological characteristics of NHL tumours in mice fed ML-1-supplemented diets were different from those in LA (control)-fed mice. The degree of mitotic activity was lower and nuclear area reduced. The degree of lymphocyte infiltration was increased in tumours from ML-1 fed mice and this was accompanied by a high incidence of apoptotic bodies. Visual observation of NHL tumours from individuals fed ML-1 diet showed a poorly developed blood supply in contrast to control-fed mice. A major reduction in number of blood capillaries in NHL tumours was confirmed by microscopic evaluation of tumour sections. The results suggested an anti-angiogenic response in ML-1-fed mice. The feeding of ML-1 compared to control diet thus provided several identifiable changes in the morphology of NHL tumours which were consistent with the observed reduction in tumour weight. There was no longer histological evidence of viable tumour in 25% mice fed the ML-1 diet for 11 days. Morphological studies of the small bowel indicated (a) that the lectin induces hyperplasia, and (b) that the lectin binds avidly to lymphoid tissue of Peyer's patches. There was evidence of limited endocytosis of the lectin. An experiment where ML-3 was added to the diet of mice three days after inoculation of tumour cells showed that the lectin was able to slow down further growth of an established tumour. The results show that ML lectins induce powerful anti-cancer effects when provided by the oral route.

Correction of the Pulfrich phenomenon by surgery and laser.

We describe 2 patients who presented with asymmetrical media changes and a spontaneous Pulfrich phenomenon. In the first case, the phenomenon was due to cataract formation and an interocular latency difference of 1.49 ms +/-0.07 (SD) was found. After cataract surgery, the symptoms resolved and no interocular latency difference could be measured. In the second case, the phenomenon was caused by posterior capsule opacification and an interocular latency difference of 1.16 +/- 0.08 ms was found. The symptoms were alleviated and no interocular latency difference could be measured after a neodymium:YAG laser capsulotomy was performed. The symptomatology of the Pulfrich phenomenon is often difficult for patients to explain. Clinicians should be aware of the phenomenon with cataract patients.

Ruptured Achilles tendons are significantly more degenerated than tendinopathic tendons.

OBJECTIVE: To ascertain whether there is an association between tendinopathic and ruptured Achilles tendons, hypothesizing that the histopathological aspects of tendinosis in tendinopathic tendons are less advanced than those found in ruptured Achilles tendons. METHODS: This was a comparative cohort study at a university teaching hospital. Histological examination was performed using hematoxylin and eosin and alcian blue/periodic acid-Schiff stained slides. The slides were interpreted using a semiquantitative grading scale assessing fiber structure, fiber arrangement, rounding of the nuclei, regional variations in cellularity, increased vascularity, decreased collagen stainability, hyalinization, and glycosaminoglycan. We calculated a pathology score giving up to three marks for each of the above variables, with 0 being normal and 3 being maximally abnormal. All the histology slides were assessed twice in a blinded manner, the agreement between two readings ranging from 0.170 to 0.750 (kappa statistics). RESULTS: We studied biopsy samples from the Achilles tendon of patients undergoing open repair for a subcutaneous rupture of their Achilles tendon (N = 35; average age (+/- SD), 48.4 +/- 16.9 yr; range, 26-80), biopsy specimens from the Achilles tendon of patients undergoing exploration for Achilles tendinopathy (N = 13; average age, 35.7 +/- 12.9 yr; range, 18-67) and specimens of Achilles tendons from individuals with no known tendon pathology (N = 16; average age, 65 +/- 19.1 yr; range, 46-82). The highest mean score of ruptured tendons was significantly greater than that of tendinopathic tendons (17.4 +/- 4.9 vs 10.5 +/- 6.1, P < 0.001), and highest mean score of tendinopathic tendons was greater that that of control tendons (10.5 +/- 6.1 vs 5.9 +/- 7.3) (P < 0.001). CONCLUSION: Ruptured and tendinopathic tendons are histologically significantly more degenerated than control tendons. The general pattern of degeneration was common to the ruptured and tendinopathic tendons, but there was a statistically significant greater degree of degeneration in the ruptured tendons. It is therefore possible that there is a common, as yet unidentified, pathological mechanism that has acted on both of these tendon populations.

Subungual glomus tumor of the hallux. A case report.

The authors report a rare case of subungual glomus tumor in the right hallux, which was excised with complete relief of symptoms. They provide a brief description of histological features and review the literature.

Light microscopic histology of achilles tendon ruptures. A comparison with unruptured tendons.

We studied biopsies from the Achilles tendons of patients undergoing open repair for a subcutaneous rupture of their Achilles tendons (27 men, 11 women; mean age, 45.3 +/- 13.8 years) and specimens of Achilles tendons from persons with no known tendon ailments (43 men, 3 women; mean age, 64.2 +/- 9.7 years). Histologic examination was performed using stained slides that were interpreted using a semiquantitative grading scale assessing fiber structure and arrangement, rounding of the nuclei, regional variations in cellularity, increased vascularity, decreased collagen stainability, hyalinization, and glycosaminoglycan. We gave up to three marks for each of these variables, with 0 being normal and 3 being maximally abnormal. All the histology slides were assessed twice in a blinded manner; the agreement between two readings ranged from 0.56 to 0.87 (kappa statistics). The score of ruptured tendons was significantly greater than the average score of control tendons (20.5 +/- 3.6 versus 6.5 +/- 2.1), and there was significantly higher degeneration in the ruptured tendons. Nonruptured Achilles tendons, even at an advanced age, and ruptured Achilles tendons are clearly part of two distinct populations. Using these staining techniques, light microscopic degeneration is not a feature of tendons from healthy, older persons.

Tenocytes from ruptured and tendinopathic achilles tendons produce greater quantities of type III collagen than tenocytes from normal achilles tendons. An in vitro model of human tendon healing.

Type I collagen is the main collagen in tendons; type III collagen is present in small amounts. Ruptured Achilles tendons contain a significantly greater proportion of type Ill collagen, which predisposes them to rupture. We used an in vitro model to determine whether tenocytes from Achilles tendons that were ruptured (N = 22), nonruptured (N = 7), tendinopathic (N = 12), and fetal (N = 8) show different behavior. Samples of Achilles tendon were digested with collagenase and the released tenocytes were collected. Primary tenocyte cultures were established and subsequently cultured onto glass coverslips. Once a confluent monolayer was obtained, the cell populations were "wounded" by scraping a pipette tip along the surface. The cultures were further incubated for either 1, 4, 8, 12, 16, or 24 hours, and production of types I and II collagen was assessed by immunostaining. In cultures from ruptured and tendinopathic tendons, there was increased production of type Ill collagen. Athletic participation places excess stress on the Achilles tendon, which could potentially lead to areas of microtrauma within the tendon. These areas may heal by the production of type III collagen, which is an abnormal healing response. Accumulation of such episodes of microtrauma could resuit in a critical point where the resistance of the tissue to tensile forces is compromised and tendon rupture occurs.