Retroauricular Region Research Articles

The Treatment Outcome of Squamous Cell Carcinoma of the External Auditory Canal and Middle Ear: A Single Institution Experience

Our results demonstrate that high in-field recurrence rate of SCC of the EAC and middle ear even treated with surgery and high dose RT. To improve the treatment outcome of this radio-resistant tumor, our study suggest that concurrent chemoradiotherapy including cisplatin regimen may have benefit for overcoming SCC of the EAC and middle ear. Futher prospective clinical trial is crucial to estimate the contribution. A retrospective review was conducted of the records of 16 patients with SCC of the EAC and middle ear between July 2003 and March 2011. The characteristics of the patients were summarized in Table 1. The median age of the patients was 62 years (range, 41―76 years). The treatment regimens of the surgery followed by concurrent chemoradiotherapy (CRT) group were intravenous cisplatin and fluorouracil (n = 1), oral tegafur gimeracil oteracil potassium (n = 2). One patients treated with definitive CRT was received oral tegafur gimeracil oteracil potassium and intravenous cisplatin. The median dose of the radiotherapy (RT) was 66 Gy (range, 50―70 Gy) at 2 Gy per fraction. Overall survival and progression-free survival rates were calculated according to the Kaplan-Meier method.

Usefulness of -Synuclein as a Marker for Early Diagnosis of Parkinson's Disease in Skin Biopsy (S22.005)

Objective: The objective was to demonstrate that the detection of α-synuclein in skin biopsies may be a useful biomarker for diagnosis of Parkinson9s disease. Background Parkinson9s disease is a progressive neurodegenerative disease characterized by: Tremor, Rigidity, Akinesia/bradykinesia and Postural changes. Atypical Parkinsonism (AP) may be initially misdiagnosed as Parkinson9s disease; the lack of an early biomarker makes the differential diagnosis difficult. Design/Methods: Sixty skin biopsies from 30 patients with Parkinsonism Syndrome; 30 were taken from the retro auricular region in cervical area, and 30 in the lower back. These were evaluated immunohistochemically with α-synuclein antibody. Its expression was compared with 20 skin biopsies of normal control subjects. Midbrain sections from a patient with Parkinson9s disease were used as positive control to determine the cut-off dilution. Results: We investigate the frequency of intranuclear inclusions in spinous cells layer (SCL) and in pilosebaceous unit (PSU)and eccrine gland (EG); the analysis of patients with PD demonstrated strong, intranuclear positivity with small nodular accumulation of 1-2 µm in diameter. The number of cells with intranuclear inclusions in PD was contrasted against AP and normal control for the SCL, PSU and EG. Differences in the expression among the three structures were significant among PD, AP and control (Kruskall-Wallis, p= Conclusions: The detection of α-synuclein in skin biopsy is an effective, inexpensive method for distinguishing Atypical Parkinsonism from Parkinson9s disease in the early stage of the disease. It could be a safe and less invasive diagnostic marker of Parkinson9s disease. Supported by: COPOCYT (Consejo Potosino de Ciencia y Tecnologia) through grant FS1611. Disclosure: Dr. Rodriguez-Leyva has received personal compensation for activities with Novartis and Boehringer Ingelheim as a speaker. Dr. Renteria-Palomo has nothing to disclose. Dr. Calderon-Garciduenas has nothing to disclose. Dr. Fuentes-Ahumada has nothing to disclose. Dr. Hernandez has nothing to disclose. Dr. Mendoza-Esquivel has nothing to disclose. Dr. Castanedo-Cazares has nothing to disclose.

Infective Dermatitis Associated With Human T-Cell Lymphotropic Virus Type 1: Evaluation of 42 Cases Observed in Bahia, Brazil

Infective dermatitis associated with human T-cell lymphotropic virus type 1 (HTLV-1; IDH) is a chronic recurrent eczema affecting HTLV-1-infected children. The epidemiological and dermatological characteristics of IDH are described, and their principal diagnostic criteria are reevaluated. Forty-two patients were included: 40 patients serologically positive for HTLV-1 and 2 seronegative patients who tested positive in polymerase chain reaction (PCR) assays. The mean age at onset of the disease was 2.6 ± 2.4 years (range, 2 months-11 years). The mean duration of breast-feeding was 24.2 months. The lesions were erythematous, scaly, and crusted, always affecting the scalp and retroauricular regions. Crusting of the nostrils was observed in 64.3% of the patients. Of the 36 patients followed up, 23 had the active disease. The age at which IDH disappeared in the others was 10-20 years. The onset of IDH may occur earlier than reported in the literature. The scalp and retroauricular regions are always affected, and lesions are invariably present in ≥3 areas. Crusting of the nostrils cannot be considered an obligatory factor for the diagnosis of IDH. The recurring nature of IDH was a characteristic found in all cases. Patients with classic IDH lesions who are serologically negative should be investigated by PCR. Therefore, the indispensable criteria for diagnosis are (1) presence of erythematous-scaly, exudative, and crusted lesions involving ≥3 areas, including the scalp and retroauricular regions; (2) recurring nature of the lesions; and (3) a finding of HTLV-1 infection by serology or molecular biology.

Primary systemic amyloidosis associated with multiple myeloma

This case report is about a 48-year-old female patient with systemic amyloidosis and multiple myeloma simultaneously. Amyloid cutaneous infiltrative lesions like papules, nodules, or plaques with a serous-hemorrhagic aspect were found in the eyelids, neck and retroauricular region, among others. She had presented intermittent papular lesions on the upper eyelids one year before, which worsened following local trauma. A local skin biopsy showed amorphous and eosinophilic substance in the dermis. Congo red staining confirmed the amyloid deposits. Abnormal exams: proteinuria (570 mg/24h), Bence-Jones proteinuria and clonal plasma cells (70%) found in myelogram. Following the diagnosis of multiple myeloma based on amyloid skin lesions, the patient was referred to the Hematology service and died 5 months after the diagnosis.

Epidermoid cyst of the outer ear: A case report and review of literature

The purpose of this article is to present a rare case of epidermoid cyst of the outer ear in a 38-year-old male patient. During clinical examination, a soft, cystic, globular, and non-tender swelling with restricted motility and well-defined margins was seen in the retroauricular region. Skin over the swelling was normal and not attached to it. The chosen treatment was total surgical removal. The histopathological findings confirmed the diagnosis of epidermoid cyst, characterized by presence of cyst cavity lined by stratified squamous epithelium with orthokeratin production. The lumen was filled with keratin. The connective tissue capsule consisted of fibrocellular stroma with numerous endothelial lined blood capillaries, which were engorged with red blood cells. The proposed treatment was considered successful, as there was no recurrence.

Management after expanded flap ulceration during auricular reconstruction

To investigate the feasibility of Brent I methods for total auricular reconstruction when expanded flap ulceration happened. The expanded flaps in the retroauricular region ulcerated during total auricular reconstruction in 8 patients with microtia. Then the expanders were removed and autologous rib cartilage frameworks were implanted. Brent I techniques for the total auricular reconstruction were employed. All the wounds in 8 patients with microtia healed primarily. The expanded flaps survived completely. The reconstructed ears had good shape and appearance with little hair. The size, shape and position of reconstructed ears were coordinated with the face. Brent I technique is an alternative method for total auricular reconstruction when the expanded flap ulceration occurs during total ear reconstruction.

Nonsurgical treatment of scalp arteriovenous malformation using a combination of ultrasound-guided thrombin injection and transarterial coil embolization

Scalp arteriovenous malformations are treated by surgical excision in many patients. We report a patient with a scalp arteriovenous malformation who was successfully treated by a combination of ultrasound-guided thrombin injection (UGTI) and transarterial coil embolization. This patient was a 52-year-old man with a subcutaneous mass in the left retroauricular region. An angiogram showed that the mass was a nidus of arteriovenous malformation. We performed UGTI after transarterial coil embolization. No recurrence or complication was reported during 2 years of follow-up. This report describes the advantages of UGTI and the method for complete occlusion of the collateral artery.

Exceedingly expanded retroauricular flaps for microtia reconstruction

The authors propose here a new strategy to obtain exceedingly expanded retroauricular mastoid skin for sufficient coverage of the three-dimensional autogenous costal cartilage framework generally used in auricular reconstruction surgery. From February 2000 to September 2009, 42 microtia reconstructions were performed using this new strategy. Auricular reconstruction was performed in three surgical stages. In the first stage, a 50-ml kidney-shaped expander was inserted subcutaneously in the retroauricular mastoid region. From 5 to 8 ml saline was then injected into the expander every 4 days until the final volume of the expander reached 100-120 ml. In the second stage, we divided the expanded mastoid skin into a superior two-third region (flap A) and an inferior one-third region (flap B, rotation flap). Autogenous costal cartilage framework was then enveloped by these expanded flaps. Tragus construction and conchal excavation was performed in the third stage. All patients were followed up from 6 months to 4 years after reconstruction. A total of 36 cases reported to be satisfied with the appearance of good shape, accurate size, right orientation, and duplication of well-detailed structures. Further revision was requested by six of the total. Complications in this series includes one case of haematoma, two cases of partial evection of the expanded skin and two cases of partial skin necrosis of the helix. All the complications were treated appropriately. Exceeding expansion can provide sufficient retroauricular non-hair-bearing skin tissues for draping the auricular cartilage framework. Skin grafts and retroauricular fascial flap are not needed any more. Patients are usually satisfied with their reconstructive auricles as regards the size, location, projection, convolution, skin-colour matching, etc. Exceedingly expanded retroauricular flaps are the appropriate envelope for the auricular cartilage framework.

Resurfacing Partial Nose Defects With a Retroauricular Skin/Cartilage Free Flap

The retroauricular skin has always received much attention by plastic surgeons for use in nose reconstruction because of its rich vascularity. Anatomically, the skin of this area lies hidden behind the ear and is very similar to that of the face. More importantly, the retroauricular skin flap along with the cartilage can be used to repair defective cartilage of the nose. All these reasons make this area an ideal donor site for nose reconstruction. This article presents the surgical procedures for reconstruction of partial nasal defects with the use of retroauricular skin/cartilage free flaps. Based on the anatomy and blood supply of the retroauricular region, a flap was designed and harvested with the retroauricular vessels as its pedicle. This flap was used to repair the partial nose defects in 10 patients, between the years 2002 and 2008. Of these, 4 patients presented with unilateral ala defects; 2 with nasal tip defects; 2 with defects on the nasal tip and bilateral ala; 1 with unilateral ala and tip defect; and 1 with unilateral ala and lateral defect. The size of the defect ranged from 2.5 × 1.5 cm to 4.0 × 3.0 cm. The flap varied between 3.0 × 2.0 cm and 4.5 × 3.5 cm. In all cases, the auricular cartilage of 1.5 × 1.0 cm to 1.0 × 0.5 cm was taken along with the flap. The retroauricular vessels were anastomosed with the facial vessels. The donor site was covered with full-thickness skin graft or local flap. No flap failure was recorded. Excellent morphologic reconstruction was obtained with these flaps with no sequela at the donor site in terms of form and function. Postoperatively, the blood supply to the flaps was fairly good in 8 cases, although there was vein congestion in 2 cases on the fourth day. However, the postoperative results of the 10 cases were satisfactory after treatment. The retroauricular skin-cartilage free flap is a good choice for partial nasal reconstruction, having the merits of a well-hidden donor site, good color match, and 1-stage operation for cartilage support and nose reconstruction.

Orbital exenteration for eyelid skin carcinoma

Exenteration of the orbit is a disfiguring and destructive procedure; it is generally performed for orbital malignancies and often provides a significant reconstructive challenge. Our purpose was to evaluate the clinical indications for orbital exenteration in a tertiary referral center and to assess the reconstructive options employed. A retrospective nonrandomized analysis was performed, selecting all patients undergoing orbital exenteration over a 5-year period, between January 2005 and January 2010. Patient demographics, tumor characteristics, and reconstructive techniques used were evaluated. Twenty patients with a mean age of 76.5 years underwent total orbital exenteration. Basal cell carcinoma was the main operative indication (45%), followed by squamous cell carcinoma (15%). Reconstructive techniques included cover of the raw orbital cavity with a temporal muscular flap in all cases followed with split skin grafting (25%), bilaterally pedicle V-Y advancement flap (10%) and a fasciocutaneous island flap of the retroauricular region (65%). Twenty percent of patients had local complications and all were treated in a satisfactory fashion. Eyelid skin tumors remain an important cause of orbital exenteration. Temporal muscle flap is a reliable and stable reconstructive solution after orbital exenteration and additional aid is supplied with skin grafts or local flaps. This technique ensures a good aesthetic outcome and better situation for later complementary treatments and minimal associated donor site morbidity.

Darier Disease Associated with HIV Infection: A Case Report

AIDS is characterized with immune dysregulation and depletion of CD4+ T cells and increased vulnerability to different pathological conditions, including many dermatoses. The present report describes features of Darier disease (DD) in an HIV-positive patient. The subject of this report was a 45-yearold Ghanaian man referred to the dermatology unit of the Iranian Red Crescent Society in Accra, Ghana. He presented with numerous follicular keratotic redbrown papules on the scalp, face, retroauricular regions, ears, sternum, upper trunk, hands, axilla, and inguinal regions. The lesions first appeared on the dorsal surface of the hands and face and subsequently appeared on the other parts of the body including the outline of the scalp. This is the first report of DD in the setting of HIV infection. Significant features of this case associated with HIV in comparison with non-HIV cases are negative family history of DD, late onset, and wide distribution of the disease without abnormality on the nails and mucous membranes beginning a few years after involvement with HIV virus.

Secondary reconstruction of burned nasal alae using rolled dermal flap with overlying full-thickness skin graft

Surgical reconstruction of the nasal tip is a very delicate procedure, as it must rebuild three different anatomical planes: mucosa, cartilage and skin with functional and aesthetic requirements. This procedure is even more difficult in burns patients, due to more limited donor sites and poor skin quality. Numerous flap options are available to reconstruct defects of the tip of the nose. The authors report their experience of nasal alar reconstruction by a scar tissue remodelling technique using a rolled dermal flap with overlying full-thickness skin graft. The medical charts of seven patients (five women and two men with a mean age of 30) treated between 1991 and 2006 were retrospectively reviewed. Six patients presented sequelae of a facial burn and one patient had congenital facial hemiagenesis. Reconstruction was bilateral for all burns patients and unilateral for the patient with facial hemiagenesis. The skin graft was raised from the medial aspect of the forearm in four cases, the retroauricular region in two cases and the groin in one case. One patient required a second surgical procedure for necrosis of the nasal tip. No nasal obstruction was reported with a mean follow-up of five years (range: six months to 15 years). The rolled dermal flap with overlying full-thickness skin graft is a simple and reliable procedure for reconstruction of the nasal alae. Filling of the nasal alae defect and reconstruction of all anatomical planes are achieved in a single surgical procedure. The aesthetic and functional results were satisfactory, with minimal scarring of the donor site. This technique is very suitable for the treatment of burn sequelae and can also be used to treat nasal hemiagenesis and nasal mutilation by biting or facial trauma.

Reversible occlusion (on–off) valves in shunted tumor patients

The first commercially produced adjustable valve for shunted hydrocephalus patients was introduced by H. Portnoy and R. Schulte in 1973. This valve is still in use and known as reversible occlusion or on-off valve. The reversible occlusion valve is mainly used in conjunction with an existing shunt in patients receiving intraventricular cytostatic therapy. The valve has a simple mechanical lock that is closed by external pressure application with a single finger. The study method is a retrospective clinical series of 15 patients undergoing a total of 16 valve implantations between 2003 and 2010 was carried out, and the valve was tested in vitro. We report a high incidence of accidental occlusions leading to a loss of consciousness in five patients (33.3%). We furthermore demonstrate in vitro that accidental occlusions can occur. The reversible occlusion valve is needed in shunted tumor patients receiving intrathecal administration of cytostatica. The mechanism works as long as no external pressure compresses the valve. However, head positions pose significant risks for unintentional occlusions. We stress the importance of: (1) a position near the midline avoiding the retroauricular or occipital regions, (2) a handling training for nurses and doctors, (3) instruction of patients and relatives, and (4) removal of the device after intrathecal cytostatic treatment.

Temporal branch of facial nerve: a normative study of nerve conduction

The temporal branch of the facial nerve is particularly vulnerable to traumatic injuries during surgical procedures. It may also be affected in clinical conditions. Electrodiagnostic studies may add additional information about the type and severity of injuries, thus allowing prognostic inferences. The objective of the present study was to develop and standardize an electrophysiological technique to specifically evaluate the temporal branch of the facial nerve. Healthy volunteers (n=115) underwent stimulation of two points along the nerve trajectory, on both sides of the face. The stimulated points were distal (on the temple, over the temporal branch) and proximal (in retro-auricular region). Activities were recorded on the ipsilateral frontalis muscle. The following variables were studied: amplitude (A), distal motor latency (DML) and conduction velocity (NCV). Differences between the sides were not significant. The proposed reference values were: A > or = 0.4 mV, DML <3.9 ms and NCV > or = 40 m/s. Variation between hemifaces should account for less than 60% for amplitudes and latency, and should be inferior to 20% for conduction velocity. These measurements are an adequate way for proposing normative values for the electrophysiological evaluation of the temporal branch.

Surgical Treatment of Relapsing Keloid of the Pinna by Fillet Flap

Background and objectives Keloid scars occur when, compared to normal healing, there is excessive formation of collagen after skin wounds or burns. Different treatments have been tried, though no particular one has been shown to be superior. The objective of this study was to assess the usefulness of the surgical technique originally described as keloid fillet flap in the management of relapsing keloids of the pinna. Material and methods The study included 10 patients (8 men, 9 white and 1 black) with a keloid on the retroauricular region or earlobe of more than 1 year duration, who had undergone previous treatment (surgery and topical or injected corticosteroids) without a good outcome or with relapse, and who had not received any treatment in the previous 6 months. Results Five patients were treated with a fillet flap procedure only, while the other 5, in addition to the procedure, also applied 5% imiquimod cream 5 times a week for 1 to 3 months. In 4 patients, no relapse was observed after the intervention. Two patients had partial flap necrosis, with subsequent partial relapse in one of these. Eighty percent reported the outcome of the procedure as good or excellent. Conclusion We achieved a response rate of 40% in the treatment of relapsing keloid of the pinna by a fillet flap procedure. This may be an alternative within the therapeutic arsenal for the treatment of relapsing keloid of the pinna, given that it does not require extensive resources and the skills needed to perform the procedure can be quickly acquired.

Expanded Retroauricular Skin and Fascial Flap in Congenital Microtia Reconstruction

The aim of this article is to report the application of expanding retroauricular skin fascia flap, and autogenous costal cartilage for congenital microtia reconstruction. Microtia reconstruction was generally completed in 3 surgical stages. In the first surgical stage, a 50 or 80 mL kidney-shaped tissue expander was inserted subcutaneously in the retroauricular mastoid region. Inflation of saline volume increased up to 60 to 80 mL, and skin flap was expanded for 2 to 3 months postoperatively. In the second surgical stage, removal of tissue expander, formation of retroauricular skin flap, elevation of retroauricular fascia flap, and pedicles of both flaps in remnant ear side were performed. Costal cartilage was harvested from ipsilateral side chest to the ear for reconstruction. The 3D ear framework was sculpted with stabilization of structure, contour and erection. Simultaneously, intermediate full thickness skin graft of 4 x 8 cm was obtained from previous incision site from where costal cartilage was harvested. Cartilage ear framework was anchored between skin flap and fascia flap, and fixed it symmetrically to the opposite normal ear, inferior portion of the ear framework was wrapped by remnant ear lobule, expanded skin flap covered the anterior portion of the framework, fascial flap was draped to the posterior side of framework and helical rim, then fascial flap was surfaced by intermediate full thickness skin graft. Suction drain was inserted and coated between skin flap and framework, drain was removed fifth postoperative day. Tragus construction and conchal excavation with skin graft was performed in the third stage of microtia reconstruction. Between October 2000 and October 2007, 426 cases were diagnosed as unilateral microtia patients and 22 cases were bilateral microtia patients. Therefore, 448 microtia ears were treated with tissue expander and autogenous costal cartilage. In 262 cases, structure of the helix, tragus, conchal excavation, auriculocepahalic angle, and symmetry to opposite normal ear were satisfied in the follow-up period of 6 months to 4 years. Antihelix, triangular fossa, and scapha were prominent with good result in most of the patients. Expanded retroauricular skin flap combined with fascial flap can cover the different size and height of cartilage ear framework in single surgical stage. At the same time, on the basis of structure stability and contour reality of cartilage framework, we can achieve fine structure and erect stability of constructed auricle. This method affords ideal results in microtia reconstruction.

Tratamiento quirúrgico del queloide recidivante de pabellón auricular mediante «colgajo en filete»

Background and objectives Keloid scars occur when, compared to normal healing, there is excessive formation of collagen after skin wounds or burns. Different treatments have been tried, though no particular one has been shown to be superior. The objective of this study was to assess the usefulness of the surgical technique originally described as keloid fillet flap in the management of relapsing keloids of the pinna. Material and methods The study included 10 patients (8 men, 9 white and 1 black) with a keloid on the retroauricular region or earlobe of more than 1 year duration, who had undergone previous treatment (surgery and topical or injected corticosteroids) without a good outcome or with relapse, and who had not received any treatment in the previous 6 months. Results Five patients were treated with a fillet flap procedure only, while the other 5, in addition to the procedure, also applied 5% imiquimod cream 5 times a week for 1 to 3 months. In 4 patients, no relapse was observed after the intervention. Two patients had partial flap necrosis, with subsequent partial relapse in one of these. Eighty percent reported the outcome of the procedure as good or excellent. Conclusion We achieved a response rate of 40% in the treatment of relapsing keloid of the pinna by a fillet flap procedure. This may be an alternative within the therapeutic arsenal for the treatment of relapsing keloid of the pinna, given that it does not require extensive resources and the skills needed to perform the procedure can be quickly acquired.

Neonatal retroauricular cellulitis as an indicator of group B streptococcal bacteremia: a case report

IntroductionThe relation between cellulitis and Group B streptococcus infection in newborns and small infants was first reported during the early 1980s and named cellulitis-adenitis syndrome. We report a case of a neonate with cellulitis-adenitis syndrome in an unusual location (retroauricular).Case presentationA 21-day-old Caucasian female infant was brought to the emergency department with fever, irritability and a decreased appetite. Physical examination revealed erythema and painful, mild swelling in the right retroauricular region. The blood count and C-reactive protein level were normal. She was treated with ceftriaxone. The fever and irritability were resolved after 24 hours, and the cellulitis was clearly reduced after two days of hospitalization. Blood culture yielded Group B streptococcus.ConclusionA thorough evaluation must be done, and lumbar punctures for infants with cellulitis must be considered. We emphasize the lack of data about acute phase reactants to predict bacteremia and meningitis and to adjust the duration of parenteral antibiotic therapy to address this syndrome.

Symmetric giant xanthogranulomas in Erdheim-Chester disease

A 33-year-old woman admitted to our hospital presenting with polyarthralgia, diabetes insipidus and xanthogranulomas in a subcutaneous precordial region and long bones was histologically diagnosed with Erdheim-Chester disease (ECD) [1]. Despite 5 years of treatment with prednisolone, cyclophosphamide and imatinib mesylate after the original diagnosis, subcutaneous xanthogranulomas again developed. F-FDG PET/CT revealed symmetric xanthogranulomas in the retroauricular regions, axillae, in tissue surrounding the psoas major muscle and in the long bones (arrows). These were histologically and immunologically confirmed as being consistent with ECD. Symmetric lesions of the long bones have generally been observed in ECD patients [2, 3]; however, our PET/CT images clearly showed symmetric cutaneous xanthogranulomas. Such symmetric anatomical changes, especially at tendon attachments or in connective tissue, may be an important clue to clarifying the aetiology of ECD.

Hiperplasia angiolinfoide como causa de eosinofilia

A hiperplasia angiolinfoide (Hale e doença de Kimura são duas entidades que podem se manifestar como nódulos, placas ou pápulas, de localização predominante em face, região retroauricular e cervical. São causas raras de eosinofilia e ainda há muita discussão em torno de suas etiopatogenias. Para alguns autores trata-se de duas patologias distintas enquanto para outros são manifestações diferentes da mesma doença. O presente artigo relata o caso de um paciente asiático que apresentava história de prurido generalizado há um ano, acompanhado de pápulas em membros e nódulo de aproximadamente 5 cm de diâmetro em região retroauricular direita com aumento progressivo. O hemograma apresentava leucocitose às custas de eosinofilia. Os achados sugerem uma superposição entre as duas patologias, pois clinicamente são sugestivos de doença de Kimura, mas a histopatologia e imuno-histoquímica confirmaram a origem endotelial da lesão, sendo compatível com Hale. Os autores destacam a raridade do caso como causa de eosinofilia, assim como alertam para a dificuldade do diagnóstico e da diferenciação entre as duas patologias.