An overview of benefits and risks of chronic melanocortin-1 receptor activation.

The melanocortin-1 receptor (MC1R) is a G protein-coupled receptor that plays a pivotal role in human skin pigmentation, melanin synthesis, redox homeostasis and inflammation. Loss-of-function MC1R variants suppress G protein-coupled receptor coupling or cell surface expression leading to a decrease in adenyl cyclase activation and intracellular levels of cyclic adenosine monophosphate. Chronic activation of MC1R can occur in certain medical conditions such as Addison's disease and physiologic states such as pregnancy melasma. MC1R activation is more commonly caused by environmental exposure to ultraviolet (UV) radiation. Approved pharmacologic melanocortin agonists that activate MC1R signalling in a targeted manner or as a bystander effect have recently become available for erythropoietic protoporphyria, sexual desire disorders, monogenic obesity and syndromic obesity. Further, small peptide analogues of α-melanocortin-stimulating hormone, human MC1R selective agonists, are photoprotective, decreasing the adverse impact of UV radiation (a primary risk factor for skin cancer) and are being investigated as potential chemoprevention strategies. MC1R activation through induction of UV-protective skin pigmentation increased DNA repair, and control of aberrant cell growth may reduce the risk of melanoma but importantly does not prevent melanoma particularly in individuals with risk factors and regular skin examination remains critical in high-risk individuals.

[Career prospects for ophthalmologists under 49 years old : A survey in Germany from 2022]. / Berufliche Zukunftsperspektive von Augenärzten unter 49 Jahren : Eine Umfrage in Deutschland aus dem Jahr 2022.

OBJECTIVE: The need for care in ophthalmology is constantly increasing due to demographic changes. The study analyzed the current professional situation and future prospects of ophthalmologists under 49 years old. METHODS: The survey of members of the German Association of Ophthalmologists (Berufsverband der Augenärzte Deutschlands) and the German Ophthalmologic Society (Deutsche Ophthalmologische Gesellschaft) was conducted in 2022. All members under the age of 49 years received an online questionnaire on the current professional situation as well as future perspectives (desired working hours, form of organization). The results of the survey were additionally compared with the 2016 survey of the German Association of Ophthalmologists. A similar questionnaire was used at that time. RESULTS: A total of 1014 people participated in the survey (62.7% women, mean age 39.3 ± 8 years, 75.6% specialists). The response rate to the survey was 25%. Specialist practice from 0 to 5 years showed a higher number of employed ophthalmologists (21% self-employed vs. 32% employed); over time the number of self-employed ophthalmologists increased (6-10 years: 40%, > 10 years: 59.3%). Overall, 46% of women were employed in a practice compared with 33% of men. Of the self-employed specialists, 95.9% said they planned to work in the same type of employment in 10 years as currently. Regarding ophthalmologists' career future, the other employment types showed a desire to move to independent practice. Compared to the 2016 survey, gender differences related to the current type of employment were evident. The number of self-employed women decreased from 43% to 26% and self-employed men decreased from 63% to 39%. The number of ophthalmologists in ambulatory healthcare centers was doubled compared to 2016. Ophthalmologists reported similar future perspectives at both survey times. CONCLUSION: The results of the survey of ophthalmologists under 49 years in Germany showed similar perceptions as in 2016. It became clear that the desire to be self-employed in 10 years is very high; however, ophthalmologists expected large practices or medical care centers to prevail in the market. The number of self-employed doctors is decreasing and the desire for self-employment is difficult to realize.

[Neuroendorine paraneoplastic syndromes]. / Neuroendokrine paraneoplastische Syndrome.

Skin is commonly affected by neuroendorine paraneoplastic syndromes (PNS). This is due to the expression of receptors in the skin by which abnormally secreted neuroendocrine hormones and mediators elicit directly, and indirectly, cutaneous key signs and thus facilitate early diagnosis of these diseases. In acromegaly, induction of the growth hormone-insulin-like growth factor­1 axis results in trophic changes of the acral portions of the skin and mucosal membranes including cutis verticis gyrata. The skin signs of non-iatrogenic Cushing syndrome are identical with those of exogenous prolonged intake of glucocorticoids: centripetal accumulation of adipose tissue, plethora and striae distensae. Episodic flushing of the face and trunk (together with explosive diarrhea) is a key feature of carcinoid tumors. Fibrotic remodeling of the heart and retroperitoneal space, and less commonly of the skin, are important complications mediated by abnormally secreted 5­hydroxytryptamine (serotonin, 5­HT), the latter eliciting profibrotic responses on HT2B-receptor-expressing fibroblasts. Androgen-secreting tumors lead to well-established receptor-mediated cutaneous signs of peripheral hyperandrogenisms: seborrhea, acne, hirsutism, and androgenetic alopecia. In contrast, the pathogenesis of necrolytic migratory erythema as a key feature of glucagonoma remains incompletely understood and is thought to be related to hypoaminoacidemia. This review summarizes the clinical features of neuroendocrine PNS with skin involvement, elucidates its underlying pathophysiology, lists differential diagnoses, and explains key diagnostic steps and principal therapeutic options. An interdisciplinary approach is essential to provide the best care of all patients with neuroendocrine PNS.

Hypophosphatemia after high-dose iron repletion with ferric carboxymaltose and ferric derisomaltose-the randomized controlled HOMe aFers study.

BACKGROUND: In patients with iron deficiency anemia, ferric carboxymaltose (FCM) and ferric derisomaltose (FDI) allow high-dose iron repletion. While FCM is reported to induce hypophosphatemia, the frequency of hypophosphatemia after an equivalent dosage of FDI had not been assessed prospectively. METHODS: In the prospective, single-center, double-blind HOMe aFers study, 26 women with iron deficiency anemia (hemoglobin < 12 g/dL plus either plasma ferritin ≤ 100 ng/mL or a plasma ferritin ≤ 300 ng/mL and transferrin saturation (TSAT) ≤ 30%) were randomized to a single intravenous infusion of 20 mg/kg body weight (up to a maximum of 1000 mg) FCM or FDI. The primary endpoint was the incidence of hypophosphatemia (plasma phosphorus levels < 2.0 mg/dL at day 1, day 7 ± 2, and/or day 35 ± 2 after the infusion). In order to investigate potential skeletal and cardiovascular implications, we assessed changes in other components of mineral and bone metabolism, left ventricular function, and arrhythmias. RESULTS: Hypophosphatemia occurred more frequently in women treated with FCM (9 out of 12 [75%]) than in those treated with FDI (1 out of 13 [8%]; p = 0.001). Within 24 h after iron supplementation, women in the FCM group had significant higher plasma intact FGF23 (p < 0.001) and lower plasma 1.25-dihydroxyvitamin D (p < 0.001). As an indicator of urinary phosphorus losses, urinary fractional phosphorus excretion was higher in the FCM group (p = 0.021 at day 7 ± 2 after iron supplementation). We did not observe differences in skeletal and cardiovascular markers, potentially because of the limited number of participants. CONCLUSIONS: While both FCM and FDI provide efficient iron repletion in participants with iron deficiency anemia, FCM induced hypophosphatemia more often than FDI. TRIAL REGISTRATION: Clinical Trials.gov NCT02905539. Registered on 8 September 2016. 2015-004808-36 (EudraCT Number) U1111-1176-4563 (WHO Universal Trial Number) DRKS00010766 (Deutsches Register Klinischer Studien).

[Update on heart failure]. / Neues zur Herzinsuffizienz.

Heart failure is one of the leading diseases in internal medicine worldwide. Because of the increase in population aging, the incidence and prevalence of heart insufficiency is rising annually and is now the most frequent individual diagnosis among hospitalized patients in Germany. The mortality rate has recently been reduced, since new pharmacological options, especially the inhibition of neprilysin, have been developed; however, heart failure is still associated with a high mortality and morbidity rate. Thus, guideline-conform treatment is of crucial importance. This review highlights and summarizes the current scientific knowledge on heart failure from 2017 and 2018 based on the guidelines of the European Society of Cardiology. New aspects about heart failure with middle grade limitations of ejection fraction are firstly presented. Subsequently, innovative diagnostic and therapeutic strategies, new pharmacological developments and handling of frequent comorbidities in patients with heart failure are discussed.

Angioplasty in asymptomatic carotid artery stenosis vs. endarterectomy compared to best medical treatment: One-year interim results of SPACE-2.

BACKGROUND: Treatment of individuals with asymptomatic carotid artery stenosis is still handled controversially. Recommendations for treatment of asymptomatic carotid stenosis with carotid endarterectomy (CEA) are based on trials having recruited patients more than 15 years ago. Registry data indicate that advances in best medical treatment (BMT) may lead to a markedly decreasing risk of stroke in asymptomatic carotid stenosis. The aim of the SPACE-2 trial (ISRCTN78592017) was to compare the stroke preventive effects of BMT alone with that of BMT in combination with CEA or carotid artery stenting (CAS), respectively, in patients with asymptomatic carotid artery stenosis of ≥70% European Carotid Surgery Trial (ECST) criteria. METHODS: SPACE-2 is a randomized, controlled, multicenter, open study. A major secondary endpoint was the cumulative rate of any stroke (ischemic or hemorrhagic) or death from any cause within 30 days plus an ipsilateral ischemic stroke within one year of follow-up. Safety was assessed as the rate of any stroke and death from any cause within 30 days after CEA or CAS. Protocol changes had to be implemented. The results on the one-year period after treatment are reported. FINDINGS: It was planned to enroll 3550 patients. Due to low recruitment, the enrollment of patients was stopped prematurely after randomization of 513 patients in 36 centers to CEA (n = 203), CAS (n = 197), or BMT (n = 113). The one-year rate of the major secondary endpoint did not significantly differ between groups (CEA 2.5%, CAS 3.0%, BMT 0.9%; p = 0.530) as well as rates of any stroke (CEA 3.9%, CAS 4.1%, BMT 0.9%; p = 0.256) and all-cause mortality (CEA 2.5%, CAS 1.0%, BMT 3.5%; p = 0.304). About half of all strokes occurred in the peri-interventional period. Higher albeit statistically non-significant rates of restenosis occurred in the stenting group (CEA 2.0% vs. CAS 5.6%; p = 0.068) without evidence of increased stroke rates. INTERPRETATION: The low sample size of this prematurely stopped trial of 513 patients implies that its power is not sufficient to show that CEA or CAS is superior to a modern medical therapy (BMT) in the primary prevention of ischemic stroke in patients with an asymptomatic carotid stenosis up to one year after treatment. Also, no evidence for differences in safety between CAS and CEA during the first year after treatment could be derived. Follow-up will be performed up to five years. Data may be used for pooled analysis with ongoing trials.

Upper-Urinary-Tract Effects After Irreversible Electroporation (IRE) of Human Localised Renal-Cell Carcinoma (RCC) in the IRENE Pilot Phase 2a Ablate-and-Resect Study.

PURPOSE: Irreversible electroporation (IRE) is a new potential ablation modality for small renal masses. Animal experiments have shown preservation of the urine-collecting system (UCS). The purpose of this clinical study was to perform the first evaluation and comparison of IRE's effects on the renal UCS by using urinary cytology, magnetic-resonance imaging, and resection histology in men after IRE of pT1a renal-cell carcinoma (RCC). METHODS: Seven patients with biopsy-proven RCC pT1a cN0cM0 underwent IRE in a phase 2a pilot ablate-and-resect study (IRENE trial). A contrast-enhanced, diffusion-weighted MRI and urinary cytology was performed 1 day before and 2, 7, and 27 days after IRE. Twenty-eight days after IRE the tumour region was completely resected surgically. RESULTS: Technical feasibility was demonstrated in all patients. In all cases, MRI revealed complete coverage of the tumour area by the ablation zone with degenerative change. The urographic late venous MRI phase (urogram scans) demonstrated normal morphological appearances. Urine cytology showed a temporary vacuolisation of the cyto- and caryoplasmas after IRE. Whereas the urothelium showed signs of regeneration 28 days after IRE-ablation, the tumour and parenchyma below it showed necrosis and permanent tissue destruction. CONCLUSIONS: Renal percutaneous IRE appears to be a safe treatment for pT1a RCC. The preservation of the UCS with unaltered normal morphology as well as urothelial regeneration and a phenomenon (new in urinary cytology) of temporary degeneration with vacuolisation of detached transitional epithelium cells were demonstrated in this clinical pilot study.

[Prognostic value of lacrimal duct diagnostics after tube removal : Retrospective analysis of risk of relapse during the first postoperative year after transcanalicular lacrimal duct surgery with silicone tubing]. / Prognostische Aussagekraft der Tränenwegsdiagnostik nach Intubatentfernung : Retrospektive Analyse des Rezidivrisikos im ersten postoperativen Jahr nach transkanalikulärer Tränenwegschirurgie mit Silikonschlauchintubation.

BACKGROUND: Transcanalicular lacrimal duct surgery has become more important over the past two decades. OBJECTIVES: The aim of the study was to prove the prognostic value of postoperative lacrimal syringing and the testing of spontaneous drainage of lacrimal fluid immediately after tube removal. METHODS: A total of 110 cases with postoperative lacrimal syringing and 183 cases with verification of the postoperative lacrimal fluid drainage performed between January 2001 and August 2008 were retrospectively evaluated. The indication for postoperative diagnostics was set by the investigator. The prognostic value of these two procedures was determined by using prognostic parameters (positive predictive value, PPV; negative predictive value, NPV) and analyzing recurrence nonexistence via Cox regression and Kaplan-Meier estimator. The observation period was limited to 12 months. Predominantly, recurrence was defined on the patient's satisfaction and absence of symptoms, which was determined with the help of a questionnaire. RESULTS: Postoperative verification of the lacrimal syringing is a suitable instrument to estimate surgical success within the first year after lacrimal surgery with a PPV of 92.31%. Testing of the spontaneous drainage of lacrimal fluid after tube removal reached a PPV of 63.33%. CONCLUSION: The proven prognostic value shows that syringing of the lacrimal duct and verification of spontaneous drainage should be integrated into postoperative care in a standardized manner. Hereby, early information for the patient about the expected result of the surgical procedure is enabled.

Regulation of melanocortin 1 receptor in allergic rhinitis in vitro and in vivo.

BACKGROUND: α-melanocyte-stimulating hormone (α-MSH) was shown to inhibit allergic airway inflammation and exert suppressive effects on human basophils. OBJECTIVE: This study aims to extend our current knowledge on the melanocortin 1 receptor (MC1R) expression in nasal tissue of patients with allergic rhinitis (AR) and functional effects of α-MSH in human basophils especially from patients with allergic rhinitis. METHODS: MC1R expression before and after nasal allergen provocation was studied in nasal mucosal tissue of AR patients and in a mouse model of allergic airway inflammation using immunofluorescence. In vitro regulation of the MC1R and CD203c surface expression on whole-blood basophils of patients with AR and controls was assessed with flow cytometry. Functional effects of α-MSH on isolated basophils were analysed regarding apoptosis with flow cytometry and chemotaxis using a Boyden chamber assay. RESULTS: We detected an accumulation of MC1R-positive basophils in nasal mucosa tissue of patients with AR 24 h after nasal allergen provocation. Such accumulation was not present in mucosa sections from healthy controls. In mice with allergic airway inflammation, we found a clear accumulation of MC1R-positive basophils in the nasal tissue compared to control mice. MC1R expression was inducible in AR patients and controls by stimulation with anti-IgE. α-MSH inhibited anti-IgE and grass pollen induced upregulation of CD203c, but had no effect on chemotaxis or apoptosis of basophils in vitro. CONCLUSIONS AND CLINICAL RELEVANCE: MC1R-positive basophils accumulate in the nasal mucosa of patients with AR after nasal allergen provocation. Since α-MSH suppresses proinflammatory effector functions in human basophils via the MC1R, it constitutes an interesting novel target for modulating the allergic inflammatory response.

Adenosine A1 receptor activation attenuates cardiac hypertrophy and fibrosis in response to α1 -adrenoceptor stimulation in vivo.

BACKGROUND AND PURPOSE: Adenosine has been proposed to exert anti-hypertrophic effects. However, the precise regulation and the role of the different adenosine receptor subtypes in the heart and their effects on hypertrophic signalling are largely unknown. We aimed to characterize expression and function of adenosine A1 receptors following hypertrophic stimulation in vitro and in vivo. EXPERIMENTAL APPROACH: Pro-hypertrophic stimuli and adenosine A1 receptor stimulation of neonatal rat cardiomyocytes and male C57/Bl6 mice, sc. drug administration, real-time PCR, (3) [H]-leucine-incorporation assay, immunostaining, tissue staining, Western blots, gravimetric analyses and echocardiography were applied in this study. KEY RESULTS: In neonatal rat cardiomyocyte cultures, phenylephrine, but not angiotensin II or insulin-like growth factor 1 (IGF1), up-regulated adenosine A1 receptors concentration-dependently. The hypertrophic phenotype (cardiomyocyte size, sarcomeric organization, total protein synthesis, c-fos expression) mediated by phenylephrine (10 µM), but not that by angiotensinII (1 µM) or IGF1 (20 ng·mL(-1) ), was counteracted by the selective A1 receptor agonist, N6-cyclopentyladenosine. In C57/BL6 mice, continuous N6-cyclopentyladenosine infusion (2 mg·kg(-1) ·day(-1) ; 21 days) blunted phenylephrine (120 mg·kg(-1) ·day(-1) ; 21 days) induced hypertrophy (heart weight, cardiomyocyte size and fetal genes), fibrosis, MMP 2 up-regulation and generation of oxidative stress - all hallmarks of maladaptive remodelling. Concurrently, phenylephrine administration increased expression of adenosine A1 receptors. CONCLUSIONS AND IMPLICATIONS: We have presented evidence for a negative feedback mechanism attenuating pathological myocardial hypertrophy following α1 -adrenoceptor stimulation. Our results suggest adenosine A1 receptors as potential targets for therapeutic strategies to prevent transition from compensated myocardial hypertrophy to decompensated heart failure due to chronic cardiac pressure overload.

Focal irreversible electroporation for prostate cancer: functional outcomes and short-term oncological control.

BACKGROUND: Current data on the use of irreversible electroporation (IRE) in the treatment of prostate cancer (PCa) is limited. We aim to evaluate the safety, short-term functional and oncological outcomes of focal IRE in low-intermediate risk PCa. METHODS: Between February 2013 and May 2014, 32 consecutive men underwent IRE at a single centre. Patients with low-intermediate risk PCa who had not received previous PCa treatment were included for analysis. The tumour was ablated using 3-6 electrodes, ensuring a minimum 5-mm safety margin around the visible magnetic resonance imaging (MRI) lesion. Follow-up included recording Clavien complications, Expanded Prostate Cancer Index Composite (EPIC) questionnaires (baseline, 1.5, 3, 6 months), 6-month multi-parametric MRI (mp-MRI) and 7-month biopsy. Findings on mp-MRI and biopsy were sub-divided into infield, adjacent or outfield of the treatment zone. RESULTS: Twenty-five men were included for final analysis. Safety follow-up revealed one Clavien Grade 3 complication and five Grade 1 complications. Functional follow-up confirmed no significant change in American Urological Association urinary symptom score, sexual or bowel function. Infield, there were no suspicious findings on mp-MRI (n=24) or biopsy (n=21) in all patients. Adjacent to the treatment zone, five (21%) had suspicious findings on mp-MRI with four (19%) proving to be significant on biopsy. Outfield, there were two (8%) with suspicious findings on mp-MRI and one (5%) significant finding on biopsy. For the five patients with significant findings on follow-up biopsy, one is awaiting repeat IRE, one had radical prostatectomy and three remained on active surveillance. CONCLUSIONS: In selected patients with low-intermediate risk PCa, focal IRE appears to be safe with minimal morbidity. There were no infield recurrences and 76% of patients were histologically free of significant cancer at 8 months. Almost all recurrences were adjacent to the treatment zone, and this was addressed by widening the treatment margins.

The Diagnostic Performance of Multiparametric Magnetic Resonance Imaging to Detect Significant Prostate Cancer.

PURPOSE: We assess the accuracy of multiparametric magnetic resonance imaging for significant prostate cancer detection before diagnostic biopsy in men with an abnormal prostate specific antigen/digital rectal examination. MATERIALS AND METHODS: A total of 388 men underwent multiparametric magnetic resonance imaging, including T2-weighted, diffusion weighted and dynamic contrast enhanced imaging before biopsy. Two radiologists used PI-RADS to allocate a score of 1 to 5 for suspicion of significant prostate cancer (Gleason 7 with more than 5% grade 4). PI-RADS 3 to 5 was considered positive. Transperineal template guided mapping biopsy of 18 regions (median 30 cores) was performed with additional manually directed cores from magnetic resonance imaging positive regions. The anatomical location, size and grade of individual cancer areas in the biopsy regions (18) as the primary outcome and in prostatectomy specimens (117) as the secondary outcome were correlated to the magnetic resonance imaging positive regions. RESULTS: Of the 388 men who were enrolled in the study 344 were analyzed. Multiparametric magnetic resonance imaging was positive in 77.0% of patients, 62.5% had prostate cancer and 41.6% had significant prostate cancer. The detection of significant prostate cancer by multiparametric magnetic resonance imaging had a sensitivity of 96%, specificity of 36%, negative predictive value of 92% and positive predictive value of 52%. Adding PI-RADS to the multivariate model, including prostate specific antigen, digital rectal examination, prostate volume and age, improved the AUC from 0.776 to 0.879 (p <0.001). Anatomical concordance analysis showed a low mismatch between the magnetic resonance imaging positive regions and biopsy positive regions (4 [2.9%]), and the significant prostate cancer area in the radical prostatectomy specimen (3 [3.3%]). CONCLUSIONS: In men with an abnormal prostate specific antigen/digital rectal examination, multiparametric magnetic resonance imaging detected significant prostate cancer with an excellent negative predictive value and moderate positive predictive value. The use of multiparametric magnetic resonance imaging to diagnose significant prostate cancer may result in a substantial number of unnecessary biopsies while missing a minimum of significant prostate cancers.

[Traumatic Lacrimal Duct Stenosis: Demographics and Success Rate of Surgical Procedures for Secondary Treatment]. / Traumatische Tränenwegsstenosen: Epidemiologie und Erfolgsraten nach sekundärer operativer Intervention.

BACKGROUND: Traumatic lacrimal duct stenosis can be the result of sharp trauma of the eyelid, indirect trauma or surgery in the nasoorbital region, as well as burns, chemotherapy and radiation of the facial region. The aim of the study is to present the demographics, patient satisfaction, and course of different surgical procedures for secondary treatment of traumatic lacrimal duct stenosis. METHODS: We retrospectively reviewed the medical records of 50 patients who required surgery for traumatic lacrimal duct stenosis from 2009 to 2011 at the University Eye Hospital in Muenster. The evaluation included the following criteria: age, sex, duration of symptoms, complication rate and the rate of recurrence. We systematically evaluated the medical data and asked the patients about the recent symptoms via telephone questionnaire. RESULTS: 60 eyes of 50 patients were included (18 women; 32 men; age: 51.8 ± 17.1 years); 34 eyes (56.7 %) had already had operations of the lacrimal system. The success rate was 58.1 %. The mean postoperative follow-up was 52.3 ± 10.7 months. In 11 cases (18.3 %), a dakryocystorhinostomy (DCR) was necessary. CONCLUSION: Traumatic lacrimal stenosis is more common in men, and has a poorer prognosis than lacrimal duct stenosis from other causes.

Soliton radiation beat analysis of optical pulses generated from two continuous-wave lasers.

We propose a fibre-based approach for generation of optical frequency combs (OFCs) with the aim of calibration of astronomical spectrographs in the low and medium-resolution range. This approach includes two steps: in the first step, an appropriate state of optical pulses is generated and subsequently moulded in the second step delivering the desired OFC. More precisely, the first step is realised by injection of two continuous-wave (CW) lasers into a conventional single-mode fibre, whereas the second step generates a broad OFC by using the optical solitons generated in step one as initial condition. We investigate the conversion of a bichromatic input wave produced by two initial CW lasers into a train of optical solitons, which happens in the fibre used as step one. Especially, we are interested in the soliton content of the pulses created in this fibre. For that, we study different initial conditions (a single cosine-hump, an Akhmediev breather, and a deeply modulated bichromatic wave) by means of soliton radiation beat analysis and compare the results to draw conclusion about the soliton content of the state generated in the first step. In case of a deeply modulated bichromatic wave, we observed the formation of a collective soliton crystal for low input powers and the appearance of separated solitons for high input powers. An intermediate state showing the features of both, the soliton crystal and the separated solitons, turned out to be most suitable for the generation of OFC for the purpose of calibration of astronomical spectrographs.

[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.

α-Melanocyte-stimulating hormone: a protective peptide against chemotherapy-induced hair follicle damage?

BACKGROUND: Effective, safe and well-tolerated therapeutic and/or preventive regimens for chemotherapy-induced alopecia (CIA) still remain to be developed. Because α-melanocyte-stimulating hormone (α-MSH) exerts a number of cytoprotective effects and is well tolerated, we hypothesized that it may be a candidate CIA-protective agent. OBJECTIVES: To explore, using a human in vitro model for chemotherapy-induced hair follicle (HF) dystrophy that employs the key cyclophosphamide metabolite (4-hydroperoxy-cyclophosphamide, 4-HC), whether α-MSH protects from 4-HC-induced HF dystrophy. METHODS: Microdissected human scalp HFs from four individuals were treated with 4-HC, α-MSH and 4-HC plus α-MSH. Changes in HF cycling, melanin distribution and hair matrix keratinocyte proliferation/apoptosis were examined by quantitative (immune-) morphometry. Expression of the cytoprotective enzyme haem oxygenase-1 (HO-1) was determined by real-time reverse transcriptase-polymerase chain reaction in HF of two individuals. RESULTS: In 50% of the individuals α-MSH reduced melanin clumping as an early sign of 4-HC-induced disruption of follicular pigmentation. α-MSH reduced 4-HC-induced apoptosis in the HFs of one female patient. These protective effects of α-MSH were not associated with changes in 4-HC-induced catagen induction. α-MSH and 4-HC both increased HO-1 mRNA expression, while the combination of both agents had additive effects on HO-1 transcription. CONCLUSIONS: Exogenous α-MSH exerts moderate HF-protective effects against 4-HC-induced human scalp HF damage and upregulates the intrafollicular expression of a key cytoprotective enzyme. However, as substantial interindividual response variations were found, further studies are needed to probe α-MSH as a candidate CIA-protective agent.