A combination of phototherapy modalities for extensive lip lesions in a patient with SARS-CoV-2 infection.

Many oral signs and symptoms related to the novel coronavirus disease (COVID-19) have been reported; however, both prevalence and etiology are still undetermined. Since the clinical features of the oral lesions seen in COVID-19 are highly heterogeneous and the treatments differ considerably in the literature, the present study aimed to report a clinical case in which a combination of antimicrobial photodynamic therapy (aPDT) and photobiomodulation therapy (PBMT) was used for extensive lip lesions in a patient suffering from COVID-19. Within 4 days and without any systemic drug administration, after two sessions of aPDT and one session of PBMT, the lip lesions were completely healed, and the patient recovered her orofacial functions satisfactorily. According to the current case report and taking into consideration the evident lack of information about many aspects of COVID-19 infection, this combination of phototherapy modalities seems to be a promising tool for managing COVID-19-related lip lesions; however, more studies are necessary.

The efficacy of synthetic pseudo-ceramide for dry and rough lips.

OBJECTIVE: Lips can easily become dry and rough, one reason being the characteristics of their ceramide (CER) profile. Lips have lower levels of total ceramides, higher percentages of CER[NS] and CER[AS], and lower percentages of CER[NP] and CER[NH] than skin in other regions of the body. The purpose of this study was to clarify the effects of synthetic pseudo-ceramide (pCer; Cetyl-PG hydroxyethyl palmitamide) to improve the dryness and roughness of the lips of healthy subjects in a formulation that exclude an occlusive effect. METHODS: Thirty-one Japanese female subjects with normal skin (age range 21-37 years; mean 28.6) were enrolled in this study. A four-week continuous use test was conducted using samples with or without 0.5% or 2.0% pCer. The degree of lip roughness was scored, and values of capacitance, transepidermal water loss (TEWL) and lip surface elasticity were measured. Endogenous CER profiles and absorption levels of pCer in the stratum corneum (SC) were analysed in tape-stripped skin specimens. RESULTS: Treatment with the pCer-2.0% sample significantly improved the visual roughness score after 2 and 4 weeks compared to 0 weeks and compared to the Blank. Moreover, an improvement in TEWL was observed after 4 weeks of treatment with the pCer-2.0% sample. CER[NP] showed a significant increase in pCer-2.0% treated lips after 4 weeks compared to the Blank. Both pCer-0.5% and pCer-2.0% were significantly absorbed after 2 weeks compared with the Blank. CONCLUSION: The effect of the synthetic pseudo-ceramide pCer to improve the roughness of lips was shown excluding the effect of occlusiveness derived from the formulation for the first time. Since the improvement of TEWL and absorption of pCer was observed, we concluded that pCer was first absorbed in rough lip areas, improved the ceramide profile and consequently restored the barrier function.

OBJECTIF: Les lèvres peuvent facilement devenir sèches et rugueuses, l'une des raisons étant les caractéristiques de leur profil de céramide (CER). Les lèvres présentent des taux plus faibles de céramides totaux, des pourcentages plus élevés de CER[NS] et de CER[AS] et des pourcentages plus faibles de CER[NP] et CER[NH] que la peau des autres régions de l'organisme. L'objectif de cette étude visait à clarifier les effets du pseudo-céramide synthétique (pCer; cétyl-PG hydroxyéthyl palmitamide) pour améliorer la sécheresse et la rugosité des lèvres de sujets en bonne santé avec une formulation excluant un effet occlusif. MÉTHODES: Trente et un sujets de sexe féminin japonais ayant une peau normale (tranche d'âge: 21 à 37 ans; moyenne: 28,6 ans) ont été inclus dans cette étude. Une analyse d'utilisation continue de quatre semaines a été effectuée en employant des échantillons avec ou sans pCer à 0,5 % ou 2,0 %. Le degré de rugosité des lèvres a été noté et les valeurs de capacitance, de perte d'eau transépidermique (transepidermal water loss, TEWL) et d'élasticité de la surface des lèvres ont été mesurées. Les profils CER endogènes et les niveaux d'absorption de pCer de la couche cornée (stratum corneum, SC) ont été analysés dans des échantillons cutanés fixés par bande adhésive. RÉSULTATS: Le traitement avec l'échantillon pCer-2,0% a amélioré de façon significative le score de rugosité visuelle après 2 et 4 semaines par rapport à 0 semaine et par rapport au groupe témoin. En outre, une amélioration de la TEWL a été observée après 4 semaines de traitement avec l'échantillon pCer-2,0%. Après 4 semaines, le CER[NP] a aumenté de manière significative dans les lèvres traitées avec pCer-2,0% par rapport au groupe témoin. Le pCer-0,5 % et le pCer-2,0% ont tous deux été absorbés de manière significative après 2 semaines par rapport au groupe témoin. CONCLUSION: L'effet du pseudo-céramide synthétique pCer pour améliorer la rugosité des lèvres a été démontré, excluant l'effet de l'occlusion dérivé de la formulation pour la première fois. Puisque l'amélioration de la TEWL et l'absorption du pCer ont été observées, nous avons conclu que le pCer était d'abord absorbé dans les zones rugueuses des lèvres, améliorait le profil du céramide et, par conséquent, rétablissait la fonction barrière.

Terapia fotodinámica con luz de día en el tratamiento de la queilitis actínica / Actinic Cheilitis Treated With Daylight Photodynamic Therapy

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A case of upper lip necrosis after cosmetic injection of hyaluronic acid soft-tissue filler-Does capillary infarction play a role in the development of vascular compromise, and what are the implications?

Facial rejuvenation with injectable filler substances is a frequently applied outpatient procedure. However, light, moderate, and even severe complications may occur. A case of tissue necrosis at the upper lip after injection of highly cross-linked hyaluronic acid together with the following salvage procedure is presented here. We discuss this complication with respect to relevant anatomy and physicochemical properties of the filler substance and review the recommendations given in literature for decreasing the likelihood of such an adverse event.

Clinical Study on the Effectiveness of Three Products in the Treatment of Herpes Simplex Labialis.

Herpes simplex labialis (HSL) is a viral disease that affects the perioral region. No guidelines recommending an effective treatment exist. The treatment of HSL with three different products was examined. Herpatch Serum, a film-forming patch, was compared to Compeed Patches, a set of semiocclusive hydrocolloid patches, and Zovirax Cream (ingredient: 5% acyclovir). In this prospective, randomized, examiner-blind study, 180 patients with recurrent HSL were split into three groups (Compeed: n = 60, Herpatch: n = 60, Zovirax: n = 60) and examined within 24 hours of HSL outbreak (DRKS Registration No.: DRKS00007786). The primary endpoint was healing time. The secondary endpoints were the reaction rate and quality of therapy evaluated by the Clinician's Global Assessment of Therapy (CGAT) and the Subject's Global Assessment of Therapy (SGAT) (0 = no response; 10 = excellent response), respectively. There was no significant difference among the healing times for the different products. The mean (95% confidence interval) was 9.67 days (9.11-10.22) for Compeed, 9.30 days (8.75-9.85) for Herpatch, and 9.80 days (9.30-10.30) for Zovirax. The reaction rate and quality of therapy (CGAT and SGAT) of Herpatch were significantly higher than those of Compeed and Zovirax. Within the study limitations, Herpatch proved to be an effective, non-antiviral alternative in the treatment of HSL.

Effect of the parasympathetic vasodilation on temperature regulation via trigeminal afferents in the orofacial area.

The skin temperature (Tm) of the orofacial area influences orofacial functions and is related to the blood flow (BF). Marked increases in BF mediated by parasympathetic vasodilation may be important for orofacial Tm regulation. Therefore, we examined the relationship between parasympathetic reflex vasodilation and orofacial Tm in anesthetized rats. Electrical stimulation of the central cut end of the lingual nerve (LN) elicited significant increases in BF and Tm in the lower lip. These increases were significantly reduced by hexamethonium, but not atropine. VIP agonist increased both BF and Tm in the lower lip. The activation of the superior cervical sympathetic trunk (CST) decreased BF and Tm in the lower lip; however, these decreases were significantly inhibited by LN stimulation. Our results suggest that parasympathetic vasodilation plays an important role in the maintaining the hemodynamics and Tm in the orofacial area, and that VIP may be involved in this response.

The efficacy of a highly occlusive formulation for dry lips.

OBJECTIVE: Since skin on the lips has a lower water content in the stratum corneum (SC) and a higher transepidermal water loss (TEWL) value than skin on the cheek, the lips are usually very dry and rough areas. Therefore, a lip balm approach to increase occlusivity of the lips is generally used to reduce water loss. Although there have been reports of an improvement effect on lip roughness by specific care agents, differences in the effects due to the occlusivity of a formulation without a specific care agent have not been reported. The purpose of this study was to clarify the improvement effect on dryness and roughness of the lips by a highly occlusive formulation consisting of a combination of common oil and wax, not by a specific care agent. METHODS: Twenty Japanese female subjects with normal skin (age range 20-39 years; mean 28.1) were enrolled in this study. A 4-week continuous use test was conducted using samples with low and high occlusivity. The degree of lip roughness and wrinkles was scored, the hollow index was assessed using ANTERA 3D images, and values of capacitance and TEWL were measured. RESULTS: The hollow index was significantly correlated with both the appearance roughness score and the wrinkle score. The sample with high occlusivity showed significant improvement in the appearance roughness score, wrinkle score, the hollow index and capacitance of the SC. In a comparison between the groups of samples with different occlusive properties, a significant improvement effect in rough appearance was seen in subjects using the highly occlusive formulation. CONCLUSION: The hollow index assessed by ANTERA 3D imaging allowed the objective evaluation of the improvement in appearance. In the case of continuous use of the highly occlusive formulation, an improvement of capacitance in the SC, which is most correlated with lip roughness, was obtained after 2 and 4 weeks. These results demonstrate for the first time that a highly occlusive formulation is effective in improving the roughness of the lips, and this effect is due to the difference in the occlusive property not by a specific care agent.

OBJECTIF: La peau qui recouvre les lèvres ayant une plus faible teneur en eau dans la couche cornée (CC) et une valeur de perte d'eau transépidermique (PETE) plus élevée que la peau des joues, les lèvres sont généralement des zones très sèches et rugueuses. Par conséquent, l'utilisation d'un baume à lèvres pour augmenter l'occlusivité des lèvres est généralement l'approche adoptée pour réduire la perte d'eau. Même s'il y a eu des rapports d'un effet d'amélioration de la rugosité des lèvres grâce à des agents de soin spécifiques, aucune différence par rapport aux effets dus aux propriétés occlusives d'une formule ne contenant pas un agent de soin spécifique n'a été rapportée. Le but de cette étude était de clarifier l'effet d'amélioration de la sécheresse et de la rugosité des lèvres d'une formule hautement occlusive composée d'une association d'huile et de cire courantes, et non pas d'un agent de soin spécifique. MÉTHODES: Vingt sujets de sexe féminin japonais ayant une peau normale (tranche d'âge : 20 à 39 ans ; moyenne : 28,1) ont été inclus dans cette étude. Un test d'utilisation continue pendant 4 semaines a été mené en utilisant des échantillons ayant des propriétés occlusives faibles et élevées. Le degré de rugosité et de ridules des lèvres a été noté, l'indice de creux a été évalué à l'aide d'images 3D ANTERA, et les valeurs de capacitance et de PETE ont été mesurées. RÉSULTATS: L'indice de creux était significativement corrélé avec le score de l'aspect de rugosité et le score de ridules. L'échantillon comportant des propriétés occlusives élevées a démontré une amélioration significative du score de l'aspect de rugosité, du score de ridules, de l'indice de creux et de la capacitance de la CC. Dans une comparaison entre les groupes d'échantillons comportant différentes propriétés occlusives, une amélioration significative de l'effet sur l'aspect rugueux a été observée chez les sujets utilisant la formule aux propriétés occlusives élevées. CONCLUSION: L'indice de creux évalué par l'imagerie 3D ANTERA a permis d'effectuer une évaluation objective de l'amélioration de l'aspect. Dans le cas d'une utilisation continue de la formule aux propriétés occlusives élevées, une amélioration de la capacitance de la CC, qui était le plus corrélée avec la rugosité des lèvres, a été atteinte au bout de 2 et 4 semaines. Ces résultats montrent pour la première fois qu'une formule aux propriétés occlusives élevées est efficace dans l'amélioration de la rugosité des lèvres, et cet effet est dû à la différence dans les propriétés occlusives et non pas à un agent de soin spécifique.

Customized lip enhancement for clinical different lip features: An observational study.

BACKGROUND: The request for lip improvement treatments with injectable hyaluronic acid (HA) is increasing. However, as the patient's needs can be extremely different, it is unconceivable to use the same technique/product for clinical different lips to grant customized results. AIMS: To provide a specific treatment approach for clinically different lips based on the Author's clinical experience. PATIENTS/METHODS: Patients belonged to four clinical groups: young lips requiring volume enhancement or a reshaping intervention, and senescent lips requiring rejuvenation or a rebuild intervention. At first visit T0, subjects underwent a pretreatment evaluation and the investigator performed an individual treatment based upon patient's esthetic goals and lip's baseline features. Lip fullness was assessed by the investigator using a Medicis Lip Fullness Scale (MLFS) at first visit (T0) and at 2 weeks (T1). Subjects and investigator answered to the Global Aesthetic Improvement Scale (GAIS) at 2 weeks T1 and at 12 weeks (T2). A photographic evaluation was undertaken at T0 and T2. RESULTS: Only, in the two groups requiring volumization there was 1 grade of improvement in the MLFS (young lips-volume and senescent lips-rebuild). Nonetheless, the performed combination of techniques/products was overall very satisfactory: 80% of the subjects reported a much improved/very much improved outcome in the GAIS, and the same was reported by the investigator in 90% of the subjects. A weak positive correlation was found between MLFS responses and subject's GAIS at T1 in all groups. CONCLUSIONS: This customized treatment approach, consisting in choosing the right gel technology injected in minimum quantities with the right technique, ensures a harmonic result avoiding aberrations and standardizations.

Effective Rejuvenation with Hyaluronic Acid Fillers: Current Advanced Concepts.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Process several patient-specific factors before reaching an optimal treatment strategy with appreciation for facial balance. 2. Define the advantages and disadvantages of various hyaluronic acid preparations and delivery techniques, to achieve a specific goal. 3. Perform advanced facial rejuvenation techniques adapted to each facial zone, combining safety considerations. 4. Prevent and treat complications caused by inadvertent intraarterial injections of hyaluronic acid. SUMMARY: The growing sophistication and diversity of modern hyaluronic acid fillers combined with an increased understanding of various delivery techniques has allowed injectable filler rejuvenation to become a customizable instrument offering a variety of different ways to improve the face: volume restoration, contouring, balancing, and feature positioning/shaping-beyond simply fading skin creases. As more advanced applications for hyaluronic acid facial rejuvenation are incorporated into practice, an increased understanding of injection anatomy is important to optimize patient safety.

Defective regression models for cure rate modeling with interval-censored data.

Regression models in survival analysis are most commonly applied for right-censored survival data. In some situations, the time to the event is not exactly observed, although it is known that the event occurred between two observed times. In practice, the moment of observation is frequently taken as the event occurrence time, and the interval-censored mechanism is ignored. We present a cure rate defective model for interval-censored event-time data. The defective distribution is characterized by a density function whose integration assumes a value less than one when the parameter domain differs from the usual domain. We use the Gompertz and inverse Gaussian defective distributions to model data containing cured elements and estimate parameters using the maximum likelihood estimation procedure. We evaluate the performance of the proposed models using Monte Carlo simulation studies. Practical relevance of the models is illustrated by applying datasets on ovarian cancer recurrence and oral lesions in children after liver transplantation, both of which were derived from studies performed at A.C. Camargo Cancer Center in São Paulo, Brazil.

Effectiveness and safety of hyaluronic acid fillers used to enhance overall lip fullness: A systematic review of clinical studies.

BACKGROUND: The majority of aesthetic treatments today are nonsurgical or minimally invasive aesthetic procedures. Soft-tissue augmentation with hyaluronic acid (HA) is one of them. Lip fullness and definition are key aesthetic factors associated with attractiveness, which is the reason that lip augmentation with HA fillers has become so popular. OBJECTIVE: To provide a systematic review of published medical literature on the effectiveness and safety of different HA fillers used to enhance overall lip fullness. METHODS AND MATERIALS: The literature search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Twenty-two studies were included in the qualitative synthesis, 9 of them with level of evidence (LOE) 1b (randomized controlled trials), 1 with LOE 2b (individual cohort study), and 12 with LOE 4 (case series, poor-quality cohort, and case-control studies). A total number of subjects included in all studies were 3965. RESULTS: Hyaluronic acid fillers turned out to be an effective and safe treatment. The assessment methods (especially for efficacy) varied greatly from one study to another. Observed responses to the treatment in studies using different lip fullness scales varied between 71% and 93.2%. The most common adverse events were local reactions at the injection sites (swelling, contusion, bruising, pain, redness, and itching). CONCLUSION: Based on the results of the studies included in this systematic review, HA fillers are effective and safe to use. The majority of included subjects were satisfied with the result and their looks.

Cannabinoid-induced lower lip retraction in rats.

RATIONALE: Lower lip retraction (LLR) in rats has been described as a distinctive effect of 5-HT1A agonists. In the course of evaluating behavioral effects of cannabinoid agonists in rats, LLR effects were evident following injection of several cannabinoid agonists. OBJECTIVES: To pharmacologically characterize cannabinoid-induced LLR in rats. METHODS: Lower lip retraction was scored using a 3-point scale for up to 6 h after injection of the cannabinoid agonists Δ9-tetrahydrocannabinol (Δ9-THC, 1-10 mg/kg), AM7499 (0.01-1.0 mg/kg), or AM2389 (0.003-0.1 mg/kg), or, for comparison, the 5-HT1A agonist 8-OH-DPAT (0.01-0.3 mg/kg). Next, antagonist effects of rimonabant (1-10 mg/kg) and WAY100635 (0.3 mg/kg) on LLR produced by cannabinoid or 5-HT1A agonists were evaluated. Lastly, effects of 8-OH-DPAT were determined following pretreatment with AM2389 (0.003-0.01 mg/kg) or Δ9-THC (1 mg/kg). RESULTS: All three cannabinoid agonists produced LLR. Effects of AM2389 were attenuated by both rimonabant and WAY100635 whereas effects of 8-OH-DPAT were antagonized by WAY 100635 but not by rimonabant. Pretreatment with 1 mg/kg Δ9-THC or 0.01 mg/kg AM2389 shifted the 8-OH-DPAT dose-effect function for LLR to the left and isobolographic analysis of the data indicates CB1 and 5-HT1A interactions can be supraadditive. CONCLUSIONS: Cannabinoid agonists produce LLR in rats, an effect heretofore ascribed only to activity at 5-HT1A receptors, via CB1 receptor-mediated actions. Co-administration of a cannabinoid agonist and the 5-HT1A agonist 8-OH-DPAT results in a synergistic effect on LLR.

High frequency ultrasound imaging as a "potential" way of evaluation modality in side effects of lip augmentation - case report.

Lip augmentation is a popular procedure performed by esthetic medicine doctors, however, it is associated with a significant number of side effects. High frequency ultrasound imaging helps with diagnosis of side effects.The patient was 43-year-old healthy female, 8 months after lip augmentation.The examination showed a variety of delayed side effects of lip augemntation. Ultrasound imaging revealed an increased echogenicity of lip soft tissue, too deep filler injection, occlusion of the inferior labial artery.

Successful treatment of isolated oral lichen planus on lower lip with traditional Chinese medicine and topical wet dressing: A case report.

RATIONALE: Biopsy is very important for the diagnosis of oral lichen planus (OLP) on the lips. Traditional Chinese medicine (TCM) can be used to coordinate the whole body, soften and eliminate swellings and masses, and regulate the functions of qi and blood. Therefore, TCM could be an effective and safe treatment for OLP. Wet dressing is particularly important for the treatment of lip diseases. We report on a rare case of OLP on the lower lip. PATIENT CONCERNS: A 38-year-old female patient presenting with a history of recurrent erosion, bleeding, and pain on her lower lip for 10 years. DIAGNOSES: Erosive OLP of the lower lip. INTERVENTIONS: The patient was treated for 4 months using TCM comprising "Qingwen Jiedu Kouyankang granules," total Paeonia glucosides, and a combination of hormones and anti-inflammatory agents applied locally using a wet dressing. OUTCOMES: Lip erosion was improved remarkably after 1 month, and there was no recurrence or aggravation of the condition. The duration of the follow-up period was 5 months. LESSONS: The therapeutics used here were effective and safe for the treatment of OLP and could improve the quality of life in patients with lip erosion. The therapeutics provide new insight into the treatment of OLP on the lip.

Dermoscopy and reflectance confocal microscopy for monitoring the treatment of actinic cheilitis with ingenol mebutate gel: Report of three cases.

Actinic cheilitis (AC) can precede the development of squamous cell carcinoma (SCC) of the lip, a location with higher risk of invasiveness and metastasis. Herein, we reported the use of ingenol mebutate (IngMeb) 0.015% gel on three consecutive days to treat three patients suffering from AC. All the three patients achieved complete clearance of AC with rapid clinical effect, favorable safety profile, good patient's compliance related to short time of applications, and few local skin reactions. So IngMeb is an attractive new therapy for AC. Moreover, the present case report adds further evidence to the usefulness of dermoscopy and Reflectance confocal microscopy (RCM) in the assessment and monitoring of treatment outcome.

Reversing the effects of 2% Lidocaine: A randomized controlled clinical trial.

OBJECTIVES: Prolonged soft tissue anesthesia following a dental appointment is a complaint that is frequently reported by patients. Soft tissue anesthesia generally exceeds the duration of pulpal anesthesia by a few hours. This can lead to difficulties with smiling, drinking, speaking and lip/cheek biting following dental appointments. Phentolamine Mesylate (PM) is a pharmacological agent capable of reducing the duration of soft tissue anesthesia following dental treatments. Many clinical trials supporting its efficacy have used sham injections compared to injections with PM. The present study aims to evaluate the effect of PM on the duration of soft tissue anesthesia compared to a control injection of saline water. METHODS: This randomized controlled trial recruited 40 participants above 18 years of age. Following an inferior alveolar nerve block using 1.8 ml of Lidocaine 2%, 1:100 000 epinephrine, participants were randomized into one of 2 groups. The test group received an injection of 0.4 mg PM (OraVerse). Participants in the control group received an injection of sterile saline water. Participants were trained in self-assessing their anesthesia, which they did until return to normal sensation. RESULTS: Thirty-six participants completed the study. PM significantly reduced the duration of soft tissue anesthesia in the lower lip (104 vs 170 min, p = .001), and tongue (83 vs 134 min, p = .004) compared to the control injection. No serious adverse events were encountered. The only adverse events observed were post-operative pain and discomfort. CONCLUSIONS: Phentolamine Mesylate hastens the return to normal soft tissue sensation and function by approximately one hour compared to a control injection of water. CLINICAL SIGNIFICANCE: Phentolamine Mesylate can be considered a safe and effective way of reducing the duration of soft tissue anesthesia following a dental appointment. This controlled clinical trial is registered at the National Institutes of Health (ClinicalTrials.gov) #NCT02861378.

Removal of Polyacrylamide Gel (Aquamid®) from the Lip as a Solution for Late-Onset Complications: Our 8-Year Experience.

BACKGROUND: The polyacrylamide hydrogel Aquamid® has been used as a permanent filler to enhance facial soft tissue volume and correct wrinkles since 2001. Various long-term studies have proved the safety of the product. Nonetheless, if complications such as migration occur, they can be difficult to treat. METHODS: Eleven patients suffering from late-onset complications after taking Aquamid® injections in the lips underwent product removal and subsequent labial reconstruction between 2009 and 2017. The reconstruction was performed using a modified bikini reduction technique combined, in eight cases, with immediate autologous fat grafting. RESULTS: In all the patients, general fibrosis and a diffused distribution of the product within all three layers of the lips resulted in the need for labial reconstruction. Migration, as far as in the mucosa and perioral skin, accounted for macroscopically visible yellowish accumulations. In ten out of eleven cases, an individually modified bikini reduction technique, with or without any combination of autologous fat grafting, led to an esthetically satisfying result. One patient developed a severe upper lip necrosis. CONCLUSION: Contradictory to several previous studies attesting to the lack of migration after Aquamid® application to the lips, capsule formation around the product is impaired, allowing for migration even years after the injection. Product aspiration is not possible in these cases, thus necessitating complex lip reconstruction. Bikini reduction and fat grafting are valuable tools for labial reconstruction. Product residuals within the mucosa have to be accepted. Special care has to be taken while treating smokers. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .