RESUMEN
Psoriasis is an inflammatory skin disease characterized by epidermal and immune dysfunctions. Although efficient, current topical treatments display adverse effects, including skin atrophy and burning sensation, leading to poor patient adherence. To overcome these downsides, pickering emulsions were formulated in which the calcitriol-containing dispersed phase was stabilized with either cyclosporin A- or tacrolimus-loaded poly(lactic-co-glycolic) acid nanoparticles. This study aimed to investigate their biological effects on lymphocytes and epidermal cells and their effectiveness in an imiquimod-induced psoriasis-like mouse model. Results showed that both emulsions significantly inhibited nuclear factor of activated T cell translocation in T lymphocytes as well as their IL-2 production, cell activation, and proliferation. In keratinocytes, inhibition of nuclear factor of activated T cell translocation decreased the production of IL-8 and TNF-α. Topical application of emulsions over skin biopsies ex vivo showed accumulation of rhodamin B-coupled poly(lactic-co-glycolic) acid nanoparticles throughout the epidermis by immunofluorescence and significantly decreased the antigen-presenting capacity of Langerhans cells in relation to a reduced expression of activation markers CD40, CD86, and HLA-DR. Using an imiquimod-induced psoriasis model in vivo, pickering emulsions significantly alleviated psoriasiform lesions potentially attributed to the decreased cutaneous expression of T-cell markers, proinflammatory cytokines, chemokines, and specific epidermal cell genes. Altogether, pickering emulsion might be a very efficient formulation for treating inflammatory dermatoses.
RESUMEN
BACKGROUND: Breast reduction surgery is a widely performed plastic surgery procedure. The incidence of such complications has been steadily decreasing in recent years but is still nonetheless 5.6%. The primary aim of this study was to analyze the incidence of the main postoperative complications of breast reduction surgery. In addition, we identified cause-and-effect links between complications and characteristics of the patients, such as smoking, age, weight resection, BMI, and wound drainage. MATERIALS AND METHODS: This retrospective study was performed on a population of 1442 women who underwent breast reduction surgery between January 2016 and October 2022 in the plastic surgery unit at Saint-Louis Hospital, Paris, France. At the follow-up examination, we evaluated the patients for complications. RESULTS: The average resection weight was 1297.7 g in a population for which the average BMI was 28.9. We found 19.9% rate of total complications, of which 3.5% were major complications. We found that only the resection weight was a risk factor for complications. DISCUSSION: The main strength of our study is the size of our sample. The large number of patients allowed us to conduct numerous analyses and obtain significant results despite the rarity of certain events. This large cohort was also responsible for the high statistical power of our results. CONCLUSION: The risk of developing a postoperative infection was 7.5% for resections of less than 2.4 kg, increasing to 13.9 % when greater than that. Thus, the administration of prophylactic antibiotic therapy to affected women to reduce the risk of infection is a distinct consideration. For the other factors, while none of them appeared to promote the occurrence of adverse events and, therefore, do not formally contraindicate breast reduction surgery, some preventive measures still strike us as being relevant, such as blade drainage, weight loss, diabetes control, and smoking cessation. LEVEL OF EVIDENCE III: 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 .
RESUMEN
BACKGROUND: Abdominoperineal resection (APR) leads to a substantial loss of tissue and a high rate of complications. The Taylor flap is a musculocutaneous flap used in reconstruction after APR. OBJECTIVES: We aimed to analyze the short and long-term morbidity of reconstruction with a Taylor flap (oblique rectus abdominis flap) after APR and to identify the risk factors for postoperative complications. METHODS: We retrospectively included all patients who had undergone APR with immediate reconstruction with a Taylor flap in our department between July 2000 and June 2018. Demographics, oncological data, treatment, and short- and long-term morbidity were reviewed. RESULTS: Among the 140 patients included, we identified early minor complications in 42 patients (30%) and 14 early major complications (10%). Total necrosis of the flap requiring its removal occurred in four patients (2.8%). Eleven patients (7.9%) presented with a midline incision hernia, and seven (5%) presented with a subcostal incision hernia. No perineal hernia was found. No risk factors for the complications were identified. CONCLUSION: The Taylor flap is a safe procedure with few complications and limited donor site morbidity. Moreover, it prevents perineal hernias. These results confirm that the Taylor flap is a well-suited procedure for reconstruction after APR.
Asunto(s)
Perineo , Procedimientos de Cirugía Plástica , Complicaciones Posoperatorias , Proctectomía , Recto del Abdomen , Humanos , Masculino , Femenino , Estudios Retrospectivos , Proctectomía/métodos , Proctectomía/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Perineo/cirugía , Persona de Mediana Edad , Anciano , Procedimientos de Cirugía Plástica/métodos , Procedimientos de Cirugía Plástica/efectos adversos , Recto del Abdomen/trasplante , Neoplasias del Recto/cirugía , Adulto , Factores de Riesgo , Anciano de 80 o más Años , Colgajo Miocutáneo/trasplante , Colgajos QuirúrgicosRESUMEN
There is a paucity of articles addressing the management strategy for perineal burns. Pelvic floor burns present a multitude of problems. These relate to the management of stool, urine, areas of maceration, significant strain, and the risk of infection. The objective of this study was to analyze a consecutive series of perineal burns by studying their characteristics, treatment, and management of urine and feces. This was a retrospective study including 100 patients between January 2018 and December 2022. The patients had all been hospitalized after suffering burns to the perineum. In 28% of the patients, the perineal burn was complicated by infection. In 61% of cases, a cutaneous infection, in 32% of cases, a urinary tract infection, in 25% of cases, a respiratory tract infection, and in 7% of cases, an infection of the digestive tract. Superinfection is associated with an increased risk of poor engraftment. A total of 100% of the patients with poor or average engraftment had an infection in the aftermath of the burn, compared with 20% of the patients with excellent engraftment and 61% of the patients with good engraftment. In our series, the analysis revealed that, in 95% of cases, no specific procedures were implemented for stool management. Perianal involvement was associated with a risk of sub-excellent engraftment. The results were statistically significant, with P = .005 and an OR = 8.72 after multivariate analysis. We favor the least invasive approach to stool management. Indications for a rectal catheter arise in patients with the following characteristics: the patient must be sedated, the burns must be deep and close to the anal opening, and the stools must be watery and abundant. In 95% of cases, we do not install a stool management device. Colostomies should remain exceptional.
Asunto(s)
Quemaduras , Perineo , Humanos , Perineo/lesiones , Quemaduras/terapia , Quemaduras/complicaciones , Estudios Retrospectivos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , AdolescenteRESUMEN
Keloid scars are hypertrophic and proliferating pathological scars extending beyond the initial lesion and without tendency to regression. Usually, keloids are considered and treated as a single entity but clinical observations suggest heterogeneity in keloid morphologies with distinction of superficial/extensive and nodular entities. Within a keloid, heterogeneity could also be detected between superficial and deep dermis or centre and periphery. Focusing on fibroblasts as main actors of keloid formation, we aimed at evaluating intra- and inter-keloid fibroblast heterogeneity by analysing their gene expression and functional capacities (proliferation, migration, traction forces), in order to improve our understanding of keloid pathogenesis. Fibroblasts were obtained from centre, periphery, papillary and reticular dermis from extensive or nodular keloids and were compared to control fibroblasts from healthy skin. Transcriptional profiling of fibroblasts identified a total of 834 differentially expressed genes between nodular and extensive keloids. Quantification of ECM-associated gene expression by RT-qPCR brought evidence that central reticular fibroblasts of nodular keloids are the population which synthesize higher levels of mature collagens, TGFß, HIF1α and αSMA as compared to control skin, suggesting that this central deep region is the nucleus of ECM production with a centrifuge extension in keloids. Although no significant variations were found for basal proliferation, migration of peripheral fibroblasts from extensive keloids was higher than that of central ones and from nodular cells. Moreover, these peripheral fibroblasts from extensive keloids exhibited higher traction forces than central cells, control fibroblasts and nodular ones. Altogether, studying fibroblast features demonstrate keloid heterogeneity, leading to a better understanding of keloid pathophysiology and treatment adaptation.
Asunto(s)
Queloide , Humanos , Queloide/metabolismo , Piel/metabolismo , Dermis/metabolismo , Fibroblastos/metabolismo , Colágeno/metabolismo , Células CultivadasRESUMEN
Natural Killer (NK) cells participate in the defense against infection by killing pathogens and infected cells and secreting immuno-modulatory cytokines. Defects in NK cell activity have been reported in obese, diabetic, and elderly patients that are at high risk of developing infected chronic wounds. Calcium alginate dressings are indicated for the debridement during the inflammatory phase of healing. Since calcium ions are major activators of NK cells, we hypothesized that these dressings could enhance NK functions, as investigated in vitro herein. Primary human blood NK cells were freshly-isolated from healthy volunteers and exposed to conditioned media (CM) from two alginate dressings, Algosteril® (ALG, pure Ca2+ alginate) and Biatain® Alginate (BIA, Ca2+ alginate with CMC), in comparison with an exogenous 3mM calcium solution. Our results demonstrated that exogenous calcium and ALG-CM, but not BIA-CM, induced NK cell activation and enhanced their capacity to kill their targets as a result of increased degranulation. NK cell stimulation by ALG depended on the influx of extracellular Ca2+ via the SOCE Ca2+ permeable plasma membrane channels. ALG-CM also activated NK cell cytokine production of IFN-γ and TNF-α through a partly Ca2+-independent mechanism. This work highlights the non-equivalence between alginate dressings for NK cell stimulation and shows that the pure calcium alginate dressing Algosteril® enhances NK cell cytotoxic and immuno-modulatory activities. Altogether, these results underline a specific property of this medical device in innate defense that is key for the cutaneous wound healing process.
Asunto(s)
Alginatos , Calcio , Humanos , Anciano , Alginatos/farmacología , Cicatrización de Heridas , Vendajes , Células Asesinas NaturalesRESUMEN
Background and Objective: Acute Achilles tendon rupture (AATR) is a common injury with a significant impact on daily living. Although various systematic reviews and meta-analyses have been written on the topic, no actual consensus exists on the best treatment. We aimed to collect the highest quality of evidence on the subject and to produce a document to which to refer, from the diagnosis to the final treatment. Material and Methods: Inclusion criteria were systematic reviews discussing Achilles tendon rupture, concerning either diagnostic criteria, classification, or treatment; English language; clearly stated inclusion and exclusion criteria for patients' selection. Results: Thirteen systematic reviews were included in the study. A strong consensus exists about the higher risk of re-rupture associated with non-operative treatment and a higher risk of complications associated with surgical repair. Conclusions: The combination of minimally invasive repair and accelerated functional rehabilitation seems to offer the best results in the treatment of Achilles tendon rupture.
Asunto(s)
Tendón Calcáneo , Traumatismos del Tobillo , Traumatismos de los Tendones , Tendón Calcáneo/lesiones , Enfermedad Aguda , Humanos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Rotura/diagnóstico , Rotura/terapia , Traumatismos de los Tendones/diagnóstico , Traumatismos de los Tendones/terapia , Resultado del TratamientoRESUMEN
BACKGROUND: The aim of this study was to describe the prevalence, characteristics and outcome of critically burn patients with pulmonary HSV reactivation. METHODS: Retrospective, single-center cohort study in a burn critical care unit in a tertiary center, including all consecutive severely burn patients with bronchoalveolar lavage performed for pneumoniae suspicion and screened for HSV from January 2013 and April 2017. We used logistic regression to identify factors associated with HSV reactivation and outcomes. RESULTS: 94 patients were included, mean age was 51 (39-64) years; median total body surface area burned was 36 (25-54)% and ICU mortality 38%. Fifty-five patients (59%) had pulmonary HSV reactivation and 30 (55%) were treated with acyclovir. Patients with HSV reactivation were more severely ill with higher SOFA score at admission compared to patient without HSV reactivation (6 [3-8] vs. 2 [1-4], p < 0.0001 respectively). In multivariate analysis, sex, SOFA score at admission and smoke inhalation were significantly associated with HSV reactivation. Only septic shock was associated with 90-day mortality when HSV reactivation was not. CONCLUSIONS: Pulmonary HSV reactivation is frequent among severely ill burn patients. Initial severity and smoke inhalation are risk factors. Antiviral treatment was not associated with outcome.
Asunto(s)
Quemaduras , Herpesviridae , Neumonía , Lesión por Inhalación de Humo , Quemaduras/complicaciones , Quemaduras/epidemiología , Quemaduras/terapia , Estudios de Cohortes , Enfermedad Crítica , Humanos , Unidades de Cuidados Intensivos , Persona de Mediana Edad , Neumonía/complicaciones , Pronóstico , Estudios Retrospectivos , Humo , Lesión por Inhalación de Humo/complicaciones , Lesión por Inhalación de Humo/epidemiologíaAsunto(s)
Mamoplastia , Transferencia de Nervios , Mama , Humanos , Regeneración Nerviosa , SensaciónRESUMEN
OBJECTIVE: There are few means to treat large keloid scars, as exeresis-even if partial-impedes direct closure without tension in the absence of a flap or a skin graft. This study evaluates the efficacy, indications for use and limitations of a new therapeutic protocol, combining an extralesional keloid excision left to heal by secondary intention with a paraffin dressing and glucocorticoid ointment, followed by monthly intrascar injections of corticosteroids upon full re-epithelialisation. METHOD: A retrospective study of patients treated for keloid scars by using the new therapeutic protocol. Scars were categorised as either healed or recurring. Their recurrence was scored according to the changes in functional signs and the scar volume. RESULTS: A total of 36 scars were studied. The mean follow-up was 14.1 months. Healing occurred in a mean of 6.8 weeks. The mean surface area was 21.6cm2. Healing rate was 30.5%. Scar volume was improved in 60% of recurrent cases and functional signs in 56%. Based on adherence with the corticotherapy, two patient groups could be discerned. For patients in the 'adherent' group, the healing rate was 40%, and scar volume was improved in 75% of recurrent cases and the functional signs in 83% of cases. CONCLUSIONS: The healing rate in this study was close to that reported in the literature. Excision-healing by secondary intention could therefore be offered to patients for whom adherence is uncertain. The protocol in this study offers a straightforward, fast, accessible solution that does not appear to entail any risk of additional keloids. It could potentially offer a treatment option in case of failure of other treatments, large keloid scars or scalp keloids.
Asunto(s)
Cicatriz/terapia , Glucocorticoides/uso terapéutico , Queloide/terapia , Colgajos Quirúrgicos , Cicatrización de Heridas , Cicatriz/cirugía , Humanos , Queloide/patología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
INTRODUCTION: Baker grade III and IV breast prosthesis capsular contractures represent a major problem for patients undergoing mammoplasties. The risk factors involved in recurrence are debated, and the best surgical approach for their prevention is not established. The objective was to identify these. MATERIALS AND METHODS: We carried out a retrospective study of patients operated on for capsular contracture at the Saint-Louis Hospital in Paris from 2012 to 2014. The characteristics at inclusion were compared so as to determine the risk factors of recurrence. The surgical approaches were compared between the patients with recurrence and those without at 5 years. RESULTS: Of the 100 patients included, 24 had a recurrence. The minimal follow-up was 5 years. No risk factors of recurrence of capsular contracture were identified. The surgical approach associated with the lowest rate of recurrence was anterior capsulectomy [OR total capsulectomy = 2.36 (0.73; 8.037) OR capsulotomy = 4.33 (1.37; 14.81)] (p < 0.040) with alteration of the volume of the implant, whether greater or less than initially [OR greater volume = 0.30 (0.096; 0.83); OR smaller volume = 0.14 (0.008; 0.85)] (p < 0.018). CONCLUSION: The occurrence of capsular contracture is a major problem with prosthetic breast surgery. The main risk factors identified to date are essentially in regard to the occurrence of a first episode. No significant risk factors for recurrence were identified. The best prevention appears to be an anterior capsulectomy with reducing the volume of the implant. 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 . IV.
Asunto(s)
Implantación de Mama , Implantes de Mama , Neoplasias de la Mama , Contractura , Mamoplastia , Implantación de Mama/efectos adversos , Implantes de Mama/efectos adversos , Contractura/epidemiología , Contractura/etiología , Contractura/prevención & control , Estudios de Seguimiento , Humanos , Contractura Capsular en Implantes/epidemiología , Contractura Capsular en Implantes/etiología , Contractura Capsular en Implantes/prevención & control , Mamoplastia/efectos adversos , Estudios RetrospectivosRESUMEN
One of the major challenges of the 21st century is the fight against aging, defined as a set of physiological mechanisms altering the physical and intellectual capacities of human beings. Aging of the skin is only one visible part of this process. It is associated with major healing defects linked in part to the alteration of the biomechanical properties of skin cells, mainly dermal fibroblasts. The immune system, another key component in maintaining skin homeostasis and the efficient healing of wounds, also suffers the effects of time: the consequent skin immunosenescence would limit the anti-infectious and vaccine response, while promoting a pro-tumor environment. The main skin damages due to aging, whether intrinsic or extrinsic, will be detailed before listing the effective anti-aging strategies to combat age-related dermal and epidermal stigmas.
TITLE: Vieillissement cutané - Physiopathologie et thérapies innovantes. ABSTRACT: Un des enjeux majeurs de ce XXIe siècle est la lutte contre le vieillissement, défini comme un ensemble de mécanismes physiologiques altérant les capacités physiques et intellectuelles de l'organisme. Le vieillissement de la peau n'est qu'un trait visible de ce processus. Il est associé à des défauts de cicatrisation majeurs liés à l'altération des propriétés biomécaniques des cellules cutanées, essentiellement des fibroblastes dermiques. Le système immunitaire, autre composante clé du maintien de l'homéostasie cutanée et du bon déroulement de la cicatrisation des plaies, subit aussi les effets du temps : l'immunosénescence cutanée consécutive limiterait la réponse anti-infectieuse et vaccinale, tout en favorisant un environnement pro-tumoral. Les principales atteintes cutanées dues au vieillissement, que celui-ci soit intrinsèque ou extrinsèque, seront détaillées avant d'énumérer les stratégies anti-âges efficaces pour lutter contre les stigmates dermiques et épidermiques liées à l'âge.
Asunto(s)
Envejecimiento de la Piel/fisiología , Terapias en Investigación/tendencias , Envejecimiento/efectos de los fármacos , Envejecimiento/fisiología , Animales , Senescencia Celular/efectos de los fármacos , Senescencia Celular/fisiología , Drogas en Investigación/farmacología , Drogas en Investigación/uso terapéutico , Epidermis/efectos de los fármacos , Epidermis/fisiología , Humanos , Piel/irrigación sanguínea , Piel/inmunología , Piel/lesiones , Piel/patología , Envejecimiento de la Piel/efectos de los fármacos , Envejecimiento de la Piel/patología , Terapias en Investigación/métodos , Cicatrización de Heridas/fisiologíaRESUMEN
BACKGROUND: Tumor molecular deciphering is crucial in clinical management. Pan-cancer next-generation sequencing panels have moved towards exhaustive molecular characterization. However, because of treatment resistance and the growing emergence of pharmacological targets, tumor-specific customized panels are needed to guide therapeutic strategies. OBJECTIVE: The objective of this study was to present such a customized next-generation sequencing panel in melanoma. METHODS: Melanoma patients with somatic molecular profiling performed as part of routine care were included. High-throughput sequencing was performed with a melanoma tailored next-generation sequencing panel of 64 genes involved in molecular classification, prognosis, theranostic, and therapeutic resistance. Single nucleotide variants and copy number variations were screened, and a comprehensive molecular analysis identified clinically relevant alterations. RESULTS: Four hundred and twenty-one melanoma cases were analyzed (before any treatment initiation for 94.8% of patients). After bioinformatic prioritization, we uncovered 561 single nucleotide variants, 164 copy number variations, and four splice-site mutations. At least one alteration was detected in 368 (87.4%) lesions, with BRAF, NRAS, CDKN2A, CCND1, and MET as the most frequently altered genes. Among patients with BRAFV600 mutated melanoma, 44.5% (77 of 173) harbored at least one concurrent alteration driving potential resistance to mitogen-activated protein kinase inhibitors. In patients with RAS hotspot mutated lesions and in patients with neither BRAFV600 nor RAS hotspot mutations, alterations constituting potential pharmacological targets were found in 56.9% (66 of 116) and 47.7% (63 of 132) of cases, respectively. CONCLUSIONS: Our tailored next-generation sequencing assay coupled with a comprehensive analysis may improve therapeutic management in a significant number of patients with melanoma. Updating such a panel and implementing multi-omic approaches will further enhance patients' clinical management.
Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Melanoma/genética , Femenino , Genotipo , Humanos , Masculino , Melanoma/patologíaRESUMEN
Restoration of a good hand function and limitation of the sequelae are the main concerns in burns treatment. The intrinsic plus position is known as the safe position for hand splinting. This article aims at describing the technique of external fixation that have been developed in Saint Louis' Burn Center in management of burned hands during the acute phase. Since 2013, a technique of external fixation has been developed in our burn center using Hoffmann II External Fixation System from Stryker® and pins from Medicalex®. External fixation of a deep burned hand is an efficient and safe way to immobilize the hand in a correct intrinsic plus position, to secure the skin grafts to improve graft take and to permit changes of the dressings without removing the immobilization device.
Asunto(s)
Quemaduras/terapia , Fijadores Externos , Traumatismos de la Mano/terapia , Vendajes , Unidades de Quemados , Femenino , Humanos , Masculino , Trasplante de Piel , Cicatrización de HeridasRESUMEN
The development of BRAF and MEK inhibitors (BRAFi/MEKi) has led to major advances in melanoma treatment. However, the emergence of resistance mechanisms limits the benefit duration and a complete response occurs in less than 20% of patients receiving BRAFi ± MEKi. In this study, we evaluated the impact of an intermittent versus continuous dosing schedule of BRAF/MEK inhibition in a melanoma model mildly sensitive to a BRAF inhibitor. The combination of a BRAFi with three different MEKi was studied with a continuous or intermittent dosing schedule in vivo, in a xenografted melanoma model and ex vivo using histoculture drug response assays (HDRAs) of patient-derived xenografts (PDX). To further understand the underlying molecular mechanisms of therapeutic efficacy, a biomarker pharmacodynamic readout was evaluated. An equal impact on tumor growth was observed in monotherapy or bitherapy regimens whether we used continuous and intermittent dosing schedules, with no significant differences in biomarkers expression between the treatments. The antitumoral effect was mostly due to modulations of expression of cell cycle and apoptotic mediators. Moreover, ex vivo studies did not show significant differences between the dosing schedules. In this context, our preclinical and pharmacodynamic results converged to show the similarity between intermittent and continuous treatments with either BRAFi or MEKi alone or with the combination of both.
RESUMEN
INTRODUCTION: In light of the concerns regarding the occurrence of anaplastic large-cell lymphoma, seromas, and scar capsules, there appears to be merit in analysis and presentation of the results of our series of inflatable smooth implants filled with saline solution, for which the follow-up was more than 10 years. PATIENTS AND METHOD: We carried out a retrospective study, including all of the patients who underwent a first breast implant for cosmetic reasons, between 2003 and 2006. RESULTS: A total of 383 patients with 766 smooth implants filled with saline solution were included in our study. No cases of lymphoma and seroma were diagnosed. Eleven patients exhibited a postoperative hematoma, and four went on to develop a capsule. Twenty-two patients (5.7%) developed a Baker Grade III or IV capsule that required revision surgery. Two patients (0.5%) opted for a bilateral prosthesis replacement due to visual rippling. In total, there were 26 (3.4%) early deflations of prostheses. DISCUSSION: There is not a statistically significant correlation between the occurrence of hematomas and the formation of a capsule. We found a lower shell rate with smooth-walled versus textured implants. The fact of having a decline of 10 years allows to be exhaustive. As for wrinkling and ripples, their occurrence has not been increased by the use of inflatable retropectoral implants. CONCLUSION: Smooth inflatable implants filled with saline solution have numerous advantages such as the possibility of a very small approach route and perioperative adaptability of the volume. In light of the lack of indication of anaplastic large-cell lymphoma with smooth implants, they are clearly an attractive alternative to textured implants filled with silicone gel. 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.