[Dorsal preservation septorhinoplasty]. / Die nasenrückenerhaltende "Dorsal-Preservation"-Septorhinoplastik.

BACKGROUND: Nasal dorsum deprojection is a very important tool in functional and aesthetic rhinoplasty. In classic techniques, resection of dorsal bone and cartilage renders dorsal reconstruction necessary. The concept of dorsal preservation rhinoplasty has been known for more than a century but has experienced a renaissance in recent years, with many critical technical modifications. MATERIALS AND METHODS: We present the latest technique of piezo-assisted dorsal preservation rhinoplasty with subdorsal triangular resection and subdorsal Cottle modification based on clinical experience of 205 cases. Furthermore, the advantages and disadvantages of this technique are discussed and several other current variations are presented. RESULTS AND DISCUSSION: Piezo-assisted osteotomy enables a very precise fracture line and sparing of periosteum, with bone sculpting possible even after mobilization. Subdorsal septal height reduction always precedes completion of the osteotomy and nasal bone mobilization, to ensure patient safety with regard to skull base injury. Using the presented technical modifications, the risk of step deformities in the radix is minimized. In selected patients, dorsal preservation septorhinoplasty enables the surgeon to perform very conservative and precise deprojection of the nose with excellent outcomes, although the spectrum of possible complications is shifted in comparison to classic techniques. CONCLUSION: The preliminary experience of 205 cases with a revision rate of less than 10% is promising. A final evaluation of the technique will only be possible after further studies and evaluation of long-term results.

Impact of COVID-19 outbreak on hospital admissions and outcome of acute coronary syndromes in a single high-volume centre in southeastern Europe.

BACKGROUND: As coronavirus disease 2019 (COVID-19) has reached pandemic status, authors from the most severely affected countries have reported reduced rates of hospital admissions for patients with acute coronary syndrome (ACS). AIM: The aim of the present study was to investigate the influence of the COVID-19 outbreak on hospital admissions and outcomes in ACS patients in a single high-volume centre in southeastern Europe. METHODS: This retrospective observational study aimed to investigate the number of hospital admissions for ACS, clinical findings at admission, length of hospitalisation, major complications and in-hospital mortality during the COVID-19 outbreak and to compare the data with the same parameters during an equivalent time frame in 2019. For the ST-elevated myocardial infarction (STEMI) subgroup of patients, changes in ischaemic times were analysed as well. RESULTS: There was a significant reduction of 44.3% in the number of patients admitted for ACS during the COVID-19 outbreak when compared with the same period in 2019 (151 vs 271; 95% confidence interval 38.4-50.2, p < 0.01) with a higher mortality rate (13.2% vs 7.2%, p = 0.03). In 2020, patients with non-ST-elevated myocardial infarction presented more often with acute heart failure (3.3% vs 0.7%, p = 0.04). During the COVID-19 outbreak, we observed increases in the total ischaemic time (303 ± 163.4 vs 200.8 ± 156.8 min, p < 0.05) and door-to-balloon time (69.2 ± 58.4 vs 50.5 ± 31.3 min, p < 0.01) in STEMI patients. CONCLUSIONS: These findings should increase the awareness of morbidity and mortality related to missed or delayed treatment of ACS among the public and the healthcare services.

Identification of the sulfotransferase iso-enzyme primarily responsible for the bio-activation of topical minoxidil.

Pattern hair loss (i.e., androgenetic alopecia) is a common condition afflicting approximately fifty percent of men and women by the age of fifty. Currently, topical minoxidil is the only US FDA approved drug for the treatment of pattern hair loss in men and women.

[Comparison of piezoelectric and conventional osteotomy in rhinoplasty : A systematic review]. / Vergleich von piezoelektrisch assistierter und konventioneller Osteotomie bei der Rhinoplastik : Ein systematisches Review.

BACKGROUND: Postoperative periorbital edema and ecchymosis after rhinoplasty are mainly caused by the osteotomy with hammer and chisel. The introduction of piezoelectric surgery could lead to a better early postoperative outcome due to improved preservation of soft tissues. The aim of this systematic review was to evaluate the methods and results of studies comparing conventional osteotomy to piezoelectric osteotomy. METHODS: A systematic literature search was conducted in the PubMed/MEDLINE and Google Scholar databases. In the primary selection, all studies on the comparison of conventional and piezoelectric osteotomies with regard to postoperative periorbital edema and/or ecchymosis were identified. Secondary selection included only study designs with a control group. RESULTS: Primary selection resulted in 15 thematically relevant publications with a notable increase in annual publications between 2007 and 2017. Six studies with control groups were selected secondarily. Qualitatively and methodologically, the studies were very heterogeneous. The results of five of the six studies indicated a significant advantage of piezo technology compared to conventional osteotomy. Only in one study was no significant difference found in the investigated postoperative outcome. CONCLUSION: Piezoelectric osteotomy resulted in a reduced propensity for postoperative edema and ecchymosis compared to the conventional osteotomy technique with a chisel. At this time, the results should be regarded as a trend. A definite recommendation favoring piezoelectric osteotomy cannot be made until more studies with higher patient numbers become available.

The effect of topical minoxidil treatment on follicular sulfotransferase enzymatic activity.

Minoxidil is the only US FDA-approved topical drug for the treatment of female and male pattern hair loss. Previously, it was demonstrated that topical minoxidil is metabolized to its active metabolite, minoxidil sulfate, by sulfotransferase enzymes located in the outer root sheath of hair follicles. The expression of sulfotransferase in the scalp varies greatly between individuals, and this difference in expression explains the varied response to minoxidil treatment. Previously, we have demonstrated the clinical utility of detecting sulfotransferase in plucked hair follicles to predict minoxidil response in pattern hair loss patients. Typically, exogenous exposure to substrates affects the expression of the enzymatic system responsible for their metabolism. For example, Phase I metabolizing enzymes, such as the cytochrome P450 family of enzymes, are known to be up-regulated in the presence of xenobiotic substrates. However, it is not known if Phase II metabolizing enzymes, such as the sulfotransferase family of enzymes, are similarly affected by the presence of substrates. In this study, we recruited 120 subjects and analyzed their sulfotransferase enzymatic activity before and after treatment with topical minoxidil. Adjusting the results for biologic (within subject) variability, we discovered that the sulfotransferase enzymatic system expression is stable over the course of minoxidil treatment. To the best of our knowledge, this is the first study to demonstrate the stability of sulfotransferase, a Phase II metabolizing enzyme, over the course of minoxidil treatment.

Low-dose daily aspirin reduces topical minoxidil efficacy in androgenetic alopecia patients.

Topical minoxidil is the only US FDA approved OTC drug for the treatment of androgenetic alopecia (AGA). Minoxidil is a pro-drug converted into its active form, minoxidil sulfate, by the sulfotransferase enzymes in the outer root sheath of hair follicles. Previously, we demonstrated that sulfotransferase activity in hair follicles predicts response to topical minoxidil in the treatment of AGA. In the human liver, sulfotransferase activity is significantly inhibited by salicylic acid. Low-dose OTC aspirin (75-81 mg), a derivative of salicylic acid, is used by millions of people daily for the prevention of coronary heart disease and cancer. It is not known whether oral aspirin inhibits sulfotransferase activity in hair follicles, potentially affecting minoxidil response in AGA patients. In the present study, we determined the follicular sulfotransferase enzymatic activity following 14 days of oral aspirin administration. In our cohort of 24 subjects, 50% were initially predicted to be responders to minoxidil. However, following 14 days of aspirin administration, only 27% of the subjects were predicted to respond to topical minoxidil. To the best of our knowledge, this is the first study to report the effect of low-dose daily aspirin use on the efficacy of topical minoxidil.

Crosstalk Between Enzyme Matrix Metalloproteinases 2 and 9 and Regulatory T Cell Immunity in the Global Burden of Atherosclerosis.

Changes in immune and inflammatory responses may play a crucial role in the development and progression of atherosclerosis, as an autoimmune, chronic and progressive inflammatory disease. Immunological activity and vascular inflammation during atherosclerosis can be modulated by autoimmune responses against self-antigens, according to changeable risk factors (cholesterol, oxidized low-density lipoprotein (ox-LDL) in the vascular wall, fatty acids, etc.), and accompanied by accumulation of leucocytes and proinflammatory cytokines, which stimulate the transcription of matrix metalloproteinases (MMPs), whose concentration are increased in foam cell-rich regions. Regulatory T cells (Tregs) represent a unique subpopulation of T cells specialized in the regulation of immune response and in the suppression of proatherogenic T cells. The aim of our study was to examine the interactions between the concentration of enzyme matrix metalloproteinases 2 and 9 (MMP-2 and 9) in urine and the percentage of Tregs in peripheral blood of two groups of patients: with carotid artery stenosis (CAS), undergoing surgery and with mild atherosclerosis (A) from general practice. The method of enzyme immunoassay (ELISA) was used to determine enzyme MMP expression, and Tregs was examined by flow cytometric analysis. Our data have showed a large increase in the enzyme MMP-2 and 9 in the urine of CAS and A patients in comparison with healthy controls and indicated this method as an easy marker for the monitoring of the development of atherosclerosis. Simultaneously, the diminished number of Tregs in the same patients pointed the importance of these regulatory mechanisms in the etiopathogenesis of atherosclerosis and possible Tregs-mediated therapy.

Melanin of the nipple areola complex.

Biological pigments or biochromes are ubiquitous in animals, plants, and simpler organisms such as fungi and bacteria. They serve a wide spectrum of functions from photosynthesis, camouflage, mimicry, photo protection from the environment to attracting mates. The human female nipple areola complex (NAC) is a highly-pigmented area. Currently, the prevailing theory as to the evolution of the pigmented human NAC is based on infant recognition of breast feeding latching zone; however, due to the protruding shape of the nipple and surrounding breast, the authors of this letter believe that the evolutionary advantage of the pigmented NAC has a direct physiological function, namely the initiation of involution at the end of the infant lactation period.

Potential risk of developing herpes simplex encephalitis in patients treated with sildenafil following primary exposure to genital herpes.

Herpes simplex encephalitis (HSE) is associated with significant mortality and morbidity. As a consequence of HSE, up to 75% of infected individuals die or experience irreversible neurological damage. While the pathogenesis of the disease is unknown, it is traditionally hypothesized that the viral infection occurs by neuronal transmission directly from peripheral sites. Non-neuronal modes of infection have generally been overlooked as the brain is protected by the blood-brain-barrier (BBB). The BBB poses an effective barrier to pathogens as well as to drugs such as chemotherapies. In the pursuit to deliver chemotherapeutic agents to the brain, several studies demonstrated that phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, may increase the permeability of the BBB enabling successful delivery of chemotherapeutic agents to the brain. In this communication, we report a case of HSE infection in a 62-year-old man, which we suspect was facilitated by the use of sildenafil during a primary genital herpes simple virus (HSV) infection. Due to large number of patients treated with PDE5 inhibitors for erectile dysfunction and the high incidence of genital HSV infection in the general population, a larger study should examine the potential risk of developing HSE in patients treated with PDE5 inhibitors.

Mechanism of action of minoxidil in the treatment of androgenetic alopecia is likely mediated by mitochondrial adenosine triphosphate synthase-induced stem cell differentiation.

Topical minoxidil is the only topical drug approved by the US Food and Drug Administration (FDA) for the treatment of androgenetic alopecia. However, the exact mechanism by which minoxidil stimulates anagen phase and promotes hair growth is not fully understood. In the late telegen phase of the hair follicle growth cycle, stem cells located in the bulge region differentiate and re-enter anagen phase, a period of growth lasting 2-6 years. In androgenetic alopecia, the anagen phase is shortened and a progressive miniaturization of hair follicles occurs, eventually leading to hair loss. Several studies have demonstrated that minoxidil increases the amount of intracellular Ca2+, which has been shown to up-regulate the enzyme adenosine triphosphate (ATP) synthase. A recent study demonstrated that ATP synthase, independent of its role in ATP synthesis, promotes stem cell differentiation. As such, we propose that minoxidil induced Ca2+ influx can increase stem cell differentiation and may be a key factor in the mechanism by which minoxidil facilitates hair growth. Based on our theory, we provide a roadmap for the development of a new class of drugs for the treatment of androgenetic alopecia.

Social selection favours offspring prone to the development of androgenetic alopecia.

In recent years, dermatologists have observed an increase in the incidence of male androgenetic alopecia (AGA). In a survey of 41 dermatologists, 88% reported an increase in incidence of AGA in men younger than 30 years. This phenomenon has no apparent explanation. However, due to the strong genetic inheritance component of AGA, a social or environmental factor which favours the inheritance of genes that increase the risk of developing AGA is suspected. To date, the strongest predictor of AGA in men has been the length of the CAG repeat located in the androgen receptor gene (AR gene) on the X chromosome. The same genetic variant in women is associated with ovulation at a later age, higher antral follicle count, and lower risk for premature ovarian failure. This led us to theorize that, due to social pressure to conceive later in life, women carriers of the short CAG repeat in the AR gene would have a selective advantage to conceive later in life and would thus favour male offspring exhibiting AGA.

Minoxidil dose response study in female pattern hair loss patients determined to be non-responders to 5% topical minoxidil.

Topical minoxidil is the only US FDA approved drug for the treatment of female pattern hair loss (FPHL). 5% minoxidil foam is only effective at re-growing hair in a minority of women (approximately 40%). Thus, the majority of FPHL patients remain untreated. Previously, we demonstrated that nonresponders to 5% minoxidil have low metabolism of minoxidil in hair follicles. As such, we hypothesized that increasing the dosage of topical minoxidil to low metabolizers would increase the number of responders without increasing the incidence of adverse events. In this study, we recruited FPHL subjects that were identified as non-responders to 5% topical minoxidil utilizing the previously validated assay for minoxidil response. Subjects were treated for 12 weeks with a novel 15% topical minoxidil solution. At 12 weeks, 60% of subjects achieved a clinically significant response based on target area hair counts (>13.7% from baseline), as well as significant improvement in global photographic assessment. None of the subjects experienced significant hemodynamic changes or any other adverse events. To the best of our knowledge, this is the first study to demonstrate the potentially beneficial effect of a higher dosage of minoxidil in FPHL subjects who fail to respond to 5% minoxidil.

Doppler laser imaging predicts response to topical minoxidil in the treatment of female pattern hair loss.

Topical minoxidil is the only drug approved by the US FDA for the treatment of female pattern hair loss. Unfortunately, following 16 weeks of daily application, less than 40% of patients regrow hair. Several studies have demonstrated that sulfotransferase enzyme activity in plucked hair follicles predicts topical minoxidil response in female pattern hair loss patients. However, due to patients’ discomfort with the procedure, and the time required to perform the enzymatic assay it would be ideal to develop a rapid, non-invasive test for sulfotransferase enzyme activity. Minoxidil is a pro-drug converted to its active form, minoxidil sulfate, by sulfotransferase enzymes in the outer root sheath of hair. Minoxidil sulfate is the active form required for both the promotion of hair regrowth and the vasodilatory effects of minoxidil. We thus hypothesized that laser Doppler velocimetry measurement of scalp blood perfusion subsequent to the application of topical minoxidil would correlate with sulfotransferase enzyme activity in plucked hair follicles. In this study, plucked hair follicles from female pattern hair loss patients were analyzed for sulfotransferase enzyme activity. Additionally, laser Doppler velocimetry was used to measure the change in scalp perfusion at 15, 30, 45, and 60 minutes, after the application of minoxidil. In agreement with our hypothesis, we discovered a correlation (r=1.0) between the change in scalp perfusion within 60 minutes after topical minoxidil application and sulfotransferase enzyme activity in plucked hairs. To our knowledge, this is the first study demonstrating the feasibility of using laser Doppler imaging as a rapid, non-invasive diagnostic test to predict topical minoxidil response in the treatment of female pattern hair loss.

[New aspects in surgery of the nasal tip]. / Neue Aspekte in der Nasenspitzenchirurgie.

The creation of both a functionally and aesthetically pleasing nasal tip contour is demanding and depends on a variety of parameters. Typically, procedures are performed with emphasis on narrowing the nasal tip structure. Excisional techniques alone inevitably lead to reduction in skeletal support and are often prone to unpredictable deformities. But long-term results of classical suture techniques have also shown unfavorable outcomes. Particularly pinching of the alae and displacement of the caudal margin of the lateral crus below the cephalic margin belong in this category. A characteristic loss of structural continuity between the domes and the alar lobule and an undesirable shadowing occur. These effects lead to an unnatural appearance of the nasal tip and frequently to impaired nasal breathing. Stability and configuration of the alar cartilages alone do not allow for an adequate evaluation of the nasal tip contour. Rather a three-dimensional approach is required in order to describe all nasal tip structures. Especially the rotational angle of the alar surface as well as the position of the lateral crus in relation to the cranial septum should be considered in the three-dimensional analysis. Taking the various parameters into account the authors present new aspects in nasal tip surgery which contribute to the creation of a functionally and aesthetically pleasing as well as durable nasal tip contour.

First Report of Stolbur Phytoplasma Associated with Maize Redness Disease of Maize in Bosnia and Herzegovina.

Maize redness (MR), caused by stolbur phytoplasma (16SrXII-A, 'Candidatus phytoplasma solani') and vectored by the cixiid planthopper Reptalus panzeri (Löw), is a severe and emerging disease of maize in southeastern Europe (2). Symptoms of MR include midrib, leaf, and stalk reddening, followed by desiccation of the entire plant, abnormal ear development, and incomplete kernel set. MR may cause significant economic losses (2). During 2010, 2011, and 2012, the presence of MR-like symptoms on maize accompanied by significant yield losses were frequently observed in maize fields in the Semberija region of northeastern Bosnia and Herzegovina. From mid-June to early July, potential vectors were collected using mouth-aspirators from maize plants in fields at three locations in the Semberija region where MR-like symptoms were previously observed. At the end of July, symptomatic maize plants were collected from six fields in the same region for phytoplasma identification. In addition, we sampled asymptomatic johnsongrass (Sorghum halepense L.), bindweed (Convolvulus arvensis L.), and volunteer wheat (Triticum aestivum L.) in areas adjacent to maize fields with MR-like symptoms, as potential phytoplasma reservoirs (2,3). A total of 49 plants (38 maize, 6 johnsongrass, 3 bindweed, and 2 wheat) and 43 R. panzeri were tested for the presence of stolbur phytoplasma. Leaves of four maize seedlings, grown in insect-proof greenhouse conditions, were used as controls. Total DNA was extracted from roots of each plant and R. panzeri using the CTAB methods (2). Initial phytoplasma detection was conducted on 16S rRNA gene using nested PCR assay with phytoplasma universal primers P1/P7 and F2n/R2 (4). Subsequently, all phytoplasma positive samples were retested employing stolbur-specific Stol11 protocol with the f2r/f3r2 primer set (1). Molecular characterization of identified phytoplasmas was performed by PCR-RFLP analysis of the tuf gene (3) and by sequence analyses of the 16S rRNA nested PCR products (GenBank Accession No. KC852868). All samples that tested positive on 16S rRNA gene using phytoplasma generic primers gave positive reaction in assays with stolbur-specific primers. Stolbur phytoplasma was identified in 36 of 49 plant samples (34 of 38 symptomatic maize plants and in 2 of 6 johnsongrass) and in 2 of 43 R. panzeri individuals. None of the control plants, bindweed, or wheat samples were positive for the presence of any phytoplasma. Tuf gene RFLP analyses enabled affiliation of all isolates to the stolbur type tuf-b. Comparison of the 16S rRNA sequence using BLAST analyses further confirmed identification of the phytoplasmas as being 'Candidatus phytoplasma solani.' The obtained sequence showed 100% identity with 'Candidatus phytoplasma solani' from corn in Serbia (JQ730750). These data clearly demonstrated association of stolbur phytoplasma with MR symptoms on maize in Semberija, which represents the first report of the MR disease and stolbur phytoplasma in maize, R. panzeri, and johnsongrass in Bosnia and Herzegovina. In the Semberija region, maize-wheat crop rotation is a traditional practice, which is a key factor for MR occurrence and persistence (2). References: (1) D. Clair et al. Vitis 42:151, 2003. (2) J. Jovic et al. Phytopathology 99:1053, 2009. (3) M. Langer and M. Maixner. Vitis 43, 191, 2004. (4) I. M. Lee et al. Int. J. Syst. Bacteriol. 48:1153, 1998.

Contemporary review on spontaneous coronary artery dissection: insights into the angiographic finding and differential diagnosis.

Spontaneous coronary artery dissection (SCAD), although in the majority of cases presents as an acute coronary syndrome (ACS), has different pathophysiology from atherosclerosis that influences specific angiography findings and enables most patients to be solved by optimal medical therapy rather than percutaneous coronary intervention (PCI). Therefore, accurate diagnosis is essential for adequate treatment of each patient as management of SCAD differs from that of ACS of atherosclerotic aetiology. So far, invasive coronary angiography remains the most important diagnostic tool in suspected SCAD. However, there are ambiguous cases that can mimic SCAD. In this review, the authors summarize current knowledge about the diagnostic algorithms, particularly angiographic features of SCAD, pitfalls of angiography, and the role of intracoronary imaging in the context of SCAD diagnosis. Finally, apart from the pathognomonic angiographic features of SCAD that are thoroughly discussed in this review, the authors focus on obscure angiography findings and findings that can mimic SCAD as well. Differential diagnosis and the timely recognition of SCAD are crucial as there are differences in the acute and long-term management of SCAD and other causes of ACS.

[Flaring spreader flaps and upper lateral advancement. Modified techniques in the reconstruction of the internal nasal valve]. / "Flaring spreader flaps" und "upper lateral advancement". Modifizierte Techniken zur Rekonstruktion der inneren Nasenklappe.

BACKGROUND: A collapse of the internal nasal valve and the formation of an inverted-V deformity represent common findings following dorsal hump removal in rhinoplasty procedures. Spreader grafts are considered as standard both in the prevention and treatment of such undesirable outcomes. The authors introduce modified surgical concepts using flaring spreader flaps and the upper lateral advancement technique to reconstruct the internal nasal valve. METHODS: After mobilization of the mucosa and separation of the upper lateral cartilages from the septum also their attachments to the nasal bones are released. The cartilages then are rotated as spreader flaps into the area of the internal nasal valve and can be used as a replacement for conventional spreader grafts. By crucial modifications of commonly applied suture techniques both the contour and airway are improved. The upper lateral advancement technique is used in cases of already present inverted-V deformities. The upper lateral cartilages are mobilized in a similar fashion and serve as attachments to usual spreader grafts. RESULTS: Flaring spreader flaps have been used in 164 patients undergoing primary rhinoplasty procedures for dorsal hump removals, the treatment of tension noses as well as deviated noses. Postoperatively all cases showed an adequate width of the middle nasal vault and pleasant dorsal aesthetic lines. No signs of an inverted-V deformity or a collapse of the internal nasal valve were present. Nasal breathing was considered significantly improved. The upper lateral advancement technique was applied in 9 patients with a present inverted-V deformity after previous rhinoplasties. During the following revision procedures an adequate reconstruction of the middle nasal vault as well as a subjectively improved airway was achieved in all cases. CONCLUSION: Both flaring spreader flaps and the upper lateral advancement technique represent reliable methods in the reconstruction of the internal nasal valve and treatment of inverted-V deformities. Moreover, flaring spreader flaps can be considered as an appropriate alternative to conventional spreader grafts in patients with only small amounts of cartilage available.