A new hope for vascular access, modifying a new technique: The Surfacer® Inside-Out Access Catheter System and sharp recanalization.

Vascular access (VA) for hemodialysis (HD) continues to be the keystone of the technique's success. The first option should be an arteriovenous fistula (AVF) or arteriovenous graft (AVG), although in some scenarios the only possibility available is a central venous catheter, which could lead to an increase in vascular complications such as thoracic central vein occlusion (TCVO), becoming a challenge for physicians. If conventional therapies cannot be performed, a new device called the Surfacer® Inside-Out® Access Catheter System (IOA) (Bluegrass Vascular Technologies, San Antonio, TX, USA) arises as a promising alternative. Here we describe the case of a patient in which we performed a combination of two techniques: sharp recanalization plus Surfacer® Inside-Out® Access Catheter System.

Inequality and the social construction of urban disaster risk in multi-hazard contexts: the case of Lima, Peru and the COVID-19 pandemic.

This field note examines the disaster risk construction process in Lima, Peru. More commonly experienced hazard contexts are considered in the light of the COVID-19 pandemic. We provide an empirical analysis based on Lima-wide data and using findings from a single case study settlement to illustrate more general conclusions. We attempt to reveal how exposure and vulnerability factors signify that very different hazards, including COVID-19, predominantly affect the same population groups. Underlying causes and drivers, all related to different expressions of urban inequality, include problems of access to suitable urban land, land trafficking and invasion, State exclusion from social housing and basic services, unsafe building practice and corruption. The research confirms the usefulness of a social construction approach to disaster risk, based on the notion of underlying causes and drivers, and the need to reconfigure urban planning processes, breaking sector silos and encouraging integrated intersectoral and interspatial approaches.

Removal of doravirine by haemodialysis in people living with HIV with end-stage renal disease.

OBJECTIVES: To evaluate the effect of haemodialysis on doravirine concentrations in people living with HIV (PLWH) undergoing routine haemodialysis. METHODS: An exploratory clinical trial that included PLWH undergoing intermittent haemodialysis was undertaken. After enrolment (day 1), doravirine 100 mg once daily was added to stable combined ART for 5 days. On day 6, blood samples were collected from each participant at the beginning and at the end of a dialysis session. Additionally, paired samples of blood entering ('in') and leaving ('out') the dialyser and the resulting dialysate were collected during the dialysis session to evaluate drug removal during dialysis. Doravirine concentrations in plasma and in the dialysate were determined by LC-MS/MS. The ratio of doravirine concentrations in plasma after/before the haemodialysis session and the haemodialysis extraction coefficient were calculated for each participant. The study was registered at https://www.clinicaltrials.gov (NCT04689737). RESULTS: Eight participants (six male) were included. The median (range) age and BMI were 49.5 (28-67) years and 23.6 (17.9-34.2) kg/m2, respectively. The doravirine dialysis extraction ratio was 34.3% (25.8%-41.4%). The ratio of doravirine concentrations in plasma after/before the haemodialysis session was 0.8 (0.6-1.0). At the end of the haemodialysis session (time post-dose 20.8-27.3 h), doravirine concentrations in plasma were 785 (101-1851) ng/mL. CONCLUSIONS: Despite moderate removal of doravirine by haemodialysis, trough doravirine concentrations in plasma after the haemodialysis sessions remained in excess of the protein-binding-adjusted EC50 (5 ng/mL). Doravirine dosage adjustments are unnecessary in PLWH undergoing intermittent haemodialysis.

Entropy Indicators: An Approach for Low-Speed Bearing Diagnosis.

To increase the competitiveness of wind energy, the maintenance costs of offshore floating and fixed wind turbines need to be reduced. One strategy is the enhancement of the condition monitoring techniques for pitch bearings, because their low operational speed and the high loads applied to them make their monitoring challenging. Vibration analysis has been widely used for monitoring the bearing condition with good results obtained for regular bearings, but with difficulties when the operational speed decreases. Therefore, new techniques are required to enhance the capabilities of vibration analysis for bearings under such operational conditions. This study proposes the use of indicators based on entropy for monitoring a low-speed bearing condition. The indicators used are approximate, dispersion, singular value decomposition, and spectral entropy of the permutation entropy. This approach has been tested with vibration signals acquired in a test rig with bearings under different health conditions. The results show that entropy indicators (EIs) can discriminate with higher-accuracy damaged bearings for low-speed bearings compared with the regular indicators. Furthermore, it is shown that the combination of regular and entropy-based indicators can also contribute to a more reliable diagnosis.

Urinary Soluble CD163 in Active Renal Vasculitis.

A specific biomarker that can separate active renal vasculitis from other causes of renal dysfunction is lacking, with a kidney biopsy often being required. Soluble CD163 (sCD163), shed by monocytes and macrophages, has been reported as a potential biomarker in diseases associated with excessive macrophage activation. Thus, we hypothesized that urinary sCD163 shed by crescent macrophages correlates with active glomerular inflammation. We detected sCD163 in rat urine early in the disease course of experimental vasculitis. Moreover, microdissected glomeruli from patients with small vessel vasculitis (SVV) had markedly higher levels of CD163 mRNA than did those from patients with lupus nephritis, diabetic nephropathy, or nephrotic syndrome. Both glomeruli and interstitium of patients with SVV strongly expressed CD163 protein. In 479 individuals, including patients with SVV, disease controls, and healthy controls, serum levels of sCD163 did not differ between the groups. However, in an inception cohort, including 177 patients with SVV, patients with active renal vasculitis had markedly higher urinary sCD163 levels than did patients in remission, disease controls, or healthy controls. Analyses in both internal and external validation cohorts confirmed these results. Setting a derived optimum cutoff for urinary sCD163 of 0.3 ng/mmol creatinine for detection of active renal vasculitis resulted in a sensitivity of 83%, specificity of 96%, and a positive likelihood ratio of 20.8. These data indicate that urinary sCD163 level associates very tightly with active renal vasculitis, and assessing this level may be a noninvasive method for diagnosing renal flare in the setting of a known diagnosis of SVV.

De novo use of a generic formulation of tacrolimus versus reference tacrolimus in kidney transplantation: evaluation of the clinical results, histology in protocol biopsies, and immunological monitoring.

The use of generic formulations of immunosuppressive drugs in renal transplantation has been and still is a controversial subject. The lack of clinical studies about safety and efficacy in transplant patients is one of the factors restricting the diffusion of generic drugs in the renal transplant field. Since March 2013, our transplant unit has incorporated generic tacrolimus (Adoport(®) ; Sandoz), replacing the one we were currently using (Prograf(®) ; Astellas). When carrying out our retrospective analysis comparing the two different formulations, we evaluated several clinical results: tacrolimus trough concentrations (C0) at 5-7 days; 1, 3, and 6 months post-transplantation; concentration/dose ratio at 6 months; acute rejection incidence; delayed graft function (DGF); renal function (as CKD-EPI); and proteinuria at 6 months in 120 patients (1:1 ratio of Prograf(®) versus Adoport(®) ), noticing no important differences. We also evaluated the results of protocol biopsies at 6 months in a subgroup of patients, thus verifying the safety and efficacy of this particular generic drug versus the reference product on a histological basis as well. No difference in the development of dnDSA (de novo donor-specific antibody) was found between the two groups.

Solar heterogeneous photo-Fenton for complete inactivation of Escherichia coli and Salmonella typhimurium in secondary-treated wastewater effluent.

In this work, complete elimination of Escherichia coli and Salmonella typhimurium was achieved in 120 min using a heterogeneous photo-Fenton process under sunlight at pH 6.5 in distilled water. A face-centered composite central design 22 with one categoric factor and three replicates at the central point was used to evaluate the effect of iron (III) oxide concentration (0.8-3.4 mg L-1), H2O2 (2-10 mg L-1), and the type of iron oxide phase (maghemite and hematite) on the inactivation of both bacteria. The results showed that the amount of catalyst, H2O2 concentration and their interaction were significant factors (p < 0.05) in the elimination of the microorganisms. Thus, under the best conditions (3.4 mg L-1 of iron (III) oxide and 10 mg L-1 of H2O2) in the experimental ranges, complete inactivation of E. coli and S. typhimurium was achieved (6-log reduction) in 120 min using the photo-Fenton treatment with both iron-oxide phases. Furthermore, the photocatalytic elimination of both bacteria by the photo-Fenton process using hematite and maghemite in secondary-treated wastewater effluent was performed obtaining slower inactivation rates (1.2-5.9 times) than in distilled water due to the matrix effect of the effluent from a wastewater treatment plant. Nevertheless, the process continued to be effective in the effluent, achieving complete bacterial elimination in 150 min using the hematite phase. Additionally, the SEM images of the bacterial cells showed that the heterogeneous photo-Fenton treatment generated permanent and irreversible cell damage, resulting in complete cell death.

Collapsing Glomerulonephritis in a Kidney Transplant Recipient after mRNA SARS-CoV-2 Vaccination.

With the vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), studies are describing cases of glomerulonephritis arising after vaccination. We present the first case of a kidney transplant patient who, after mRNA vaccination against SARS-CoV-2, developed nephrotic proteinuria and renal dysfunction, with a biopsy diagnostic of collapsing glomerulonephritis. No other triggers for this glomerulonephritis were identified. Antibodies against the spike protein were negative, but the patient developed a specific T-cell response. The close time between vaccination and the proteinuria suggests a possible determinant role of vaccination. We should be aware of nephropathies appearing after COVID-19 vaccination in kidney transplant recipients also.

Depressive symptomatology in adults during the COVID-19 pandemic.

Depression entails changes in the mental health of individuals worldwide. Episodes of depression lead to mood swings and changes in the motivational dimension. Our research focused on the prevalence of depression in the adult population and on how it affected the social and affective dimensions. Owing to the current pandemic, we deemed it necessary to explore how protective measures against COVID-19 infection, such as quarantines, could be related to mental health. Moreover, we found it important to determine the prevalence of depressive and anxious symptomatology in adults from the Valle del Cauca region in Colombia during the social isolation connected to COVID-19. Our study was descriptive, analytical and cross-sectional, and involved 1248 subjects. As tools, we used the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale. The data demonstrated that women were more likely to display symptoms of depression and that individuals aged between 24 and 29 were less likely to reveal symptoms of anxiety than those aged between 18 and 23. Moreover, childless or economically dependent individuals proved to be more likely to display symptoms of depression during the pandemic.

Treatment for severe COVID-19 with a biomimetic sorbent haemoperfusion device in patients on haemodialysis.

Haemodialysis (HD) patients present more morbidity and mortality risk in coronavirus disease 2019 (COVID-19). In patients who may develop severe symptoms, the process called 'viral sepsis' seems to be a crucial mechanism. In those cases, the HD procedure provides an excellent tool to explore the benefit of some extracorporeal therapies. We reported the outcome of four HD patients with severe COVID-19 treated with Seraph®100 haemoperfusion (HP) device. Three of the four cases presented a good clinical response after HP. In conclusion, the treatment with Seraph®100 device may be a simultaneous treatment to improve HD patients with severe acute respiratory syndrome coronavirus 2.

Impact of obesity on the evolution of outcomes in peritoneal dialysis patients.

BACKGROUND: Some studies reveal that obesity is associated with a decrease in mortality in haemodialysis (HD) patients. However, few studies have addressed the association between body mass index (BMI) and peritoneal dialysis (PD) patients. METHODS: We performed this longitudinal, retrospective study to evaluate the impact of obesity on PD patients, using data from the Catalan Registry of Renal Patients from 2002 to 2015 (n = 1573). Obesity was defined as BMI ≥30; low weight: BMI <18.5; normal range: BMI = 18.5-24.99; and pre-obesity: BMI = 25-29.99 kg/m2. Variations in BMI were calculated during follow-up. The main outcomes evaluated were the technique and patient survival. RESULTS: Obesity was observed in 20% of patients starting PD. We did not find differences in sex or PD modality, with the obesity group being older (65.9% are ≥55 years versus 59% non-obese, P = 0.003) and presenting more diabetes mellitus and cardiovascular disease (CVD) (47.9% obese versus 25.1% non-obese and 41.7% versus 31.5%, respectively). We did not observe differences in haemoglobin, albumin and Kt/V in obese patients. Regarding peritonitis rate, we did not find any difference between groups, presenting more peritonitis patients on continuous ambulatory peritoneal dialysis and aged ≥65 years [sub-hazard ratio (SHR) = 1.75, P = 0.000 and SHR = 1.56, P = 0.009]. In relation to technique survival, we found higher transfer to HD in the obese group of patients in the univariate analysis, which was not confirmed in the multivariate analysis (SHR = 1.12, P = 0.4), and we did not find differences in mortality rate. In relation to being transplanted, the underweight group, elderly and patients with CVD or diabetic nephropathy presented less probability to undergo kidney transplantation (SHR = 0.65, 0.24, 0.5 and 0.54, P < 0.05). Obese patients did not present differences in survival with weight changes but in normal-weight patients, a gain of 7% of the basal weight during the first year had a protective effect on death risk (hazard ratio 0.6, P = 0.034). CONCLUSIONS: Obese and non-obese patients starting on PD had similar outcomes.

Mechanically transduced immunosorbent assay to measure protein-protein interactions.

Measuring protein-protein interaction (PPI) affinities is fundamental to biochemistry. Yet, conventional methods rely upon the law of mass action and cannot measure many PPIs due to a scarcity of reagents and limitations in the measurable affinity ranges. Here, we present a novel technique that leverages the fundamental concept of friction to produce a mechanical signal that correlates to binding potential. The mechanically transduced immunosorbent (METRIS) assay utilizes rolling magnetic probes to measure PPI interaction affinities. METRIS measures the translational displacement of protein-coated particles on a protein-functionalized substrate. The translational displacement scales with the effective friction induced by a PPI, thus producing a mechanical signal when a binding event occurs. The METRIS assay uses as little as 20 pmols of reagents to measure a wide range of affinities while exhibiting a high resolution and sensitivity. We use METRIS to measure several PPIs that were previously inaccessible using traditional methods, providing new insights into epigenetic recognition.

Progress in the Development and Challenges for the Use of Artificial Kidneys and Wearable Dialysis Devices.

BACKGROUND: Renal transplantation is the treatment of choice for chronic kidney disease (CKD) patients, but the shortage of kidneys and the disabling medical conditions these patients suffer from make dialysis essential for most of them. Since dialysis drastically affects the patients' lifestyle, there are great expectations for the development of wearable artificial kidneys, although their use is currently impeded by major concerns about safety. On the other hand, dialysis patients with hemodynamic instability do not usually tolerate intermittent dialysis therapy because of their inability to adapt to a changing scenario of unforeseen events. Thus, the development of novel wearable dialysis devices and the improvement of clinical tolerance will need contributions from new branches of engineering such as artificial intelligence (AI) and machine learning (ML) for the real-time analysis of equipment alarms, dialysis parameters, and patient-related data with a real-time feedback response. These technologies are endowed with abilities normally associated with human intelligence such as learning, problem solving, human speech understanding, or planning and decision-making. Examples of common applications of AI are visual perception (computer vision), speech recognition, and language translation. In this review, we discuss recent progresses in the area of dialysis and challenges for the use of AI in the development of artificial kidneys. SUMMARY AND KEY MESSAGES: Emerging technologies derived from AI, ML, electronics, and robotics will offer great opportunities for dialysis therapy, but much innovation is needed before we achieve a smart dialysis machine able to analyze and understand changes in patient homeostasis and to respond appropriately in real time. Great efforts are being made in the fields of tissue engineering and regenerative medicine to provide alternative cell-based approaches for the treatment of renal failure, including bioartificial renal systems and the implantation of bioengineered kidney constructs.

Hallazgos mastográficos benignos que simulan malignidad: un dilema diagnóstico / Benign mammographic findings that simulate malignancy: a diagnostic dilemma

Resumen OBJETIVO: Identificar los principales hallazgos histopatológicos benignos y determinar la tasa de falsos positivos que suelen causar conflicto al categorizar las mastografías en el sistema BI-RADS por su aspecto, que puede simular un proceso maligno. MATERIALES Y MÉTODOS: Estudio de cohorte, retrospectivo, efectuado en pacientes atendidas en la Unidad Médica de Alta Especialidad 4 Luis Castelazo Ayala (2019-2023) con reporte mastográfico alterado o sospecha clínica de malignidad. Para el análisis estadístico se utilizó el programa JASP 2.0 y χ2 para la diferencia de proporciones entre grupos. RESULTADOS: De un grupo de 11,481 pacientes, se reportaron 1643 mastografías alteradas: 444 con reportes falsos positivos, 23 pacientes con sospecha clínica y exclusión de 16 que no cumplieron con los criterios de inclusión establecidos. La muestra poblacional estudiada fue de 451 pacientes. La mayoría permaneció asintomática al momento del estudio (42.1%). El hallazgo histopatológico benigno con mayor prevalencia fue el fibroadenoma y su síntoma más relevante el nódulo palpable. La tasa de falsos positivos fue de 4.3%. CONCLUSIONES: En la actualidad, gracias a la implementación de programas de tamizaje es posible establecer diagnósticos de cáncer de mama en etapas tempranas, aunque con la desventaja que el reporte puede resultar falso positivo y ello dar lugar a incremento de la morbilidad y sobretratamiento. Los estándares internacionales indican que estos no deben sobrepasar el 10%.

Abstract OBJECTIVE: To identify the main benign histopathological findings that often cause conflict when categorizing mastographies in the BI-RADS system due to their appearance, which may simulate a malignant process and false positive rate. MATERIALS AND METHODS: Retrospective cohort study carried out in patients attended at the Unidad Médica de Alta Especialidad 4 Luis Castelazo Ayala (2019-2023) with an altered mastographic report or clinical suspicion of malignancy. For statistical analysis we used the JASP 2.0 programme and χ2 for the difference in proportions between groups. RESULTS: From a group of 11,481 patients, 1,643 altered mastograms were reported: 444 with false positive reports, 23 patients with clinical suspicion and exclusion of 16 who did not meet the established inclusion criteria. The population sample studied was 451 patients. The majority remained asymptomatic at the time of the study (42.1%). The most prevalent benign histopathological finding was fibroadenoma and the most relevant symptom was a palpable nodule. The false positive rate was 4.3%. CONCLUSIONS: Currently, thanks to the implementation of screening programmes it is possible to establish breast cancer diagnoses in early stages, although with the disadvantage that the report may be false positive and this may lead to increased morbidity and overtreatment. International standards indicate that these should not exceed 10%.

Efficacy of mycophenolate treatment in adults with steroid-dependent/frequently relapsing idiopathic nephrotic syndrome.

BACKGROUND: This study assessed the efficacy of therapy with mycophenolate (MF) and reduced doses of steroids in adults with steroid-dependent/frequently relapsing idiopathic nephrotic syndrome (SD/FR-INS). METHODS: Twenty-nine nephrotic patients (including 16 males and 13 females; mean age: 40 years, range: 18-74) were treated. Starting doses of MF were 2000 mg/day for mofetil MF (1500 mg/day in one patient) or 1440 mg/day for sodium MF. The initial prednisone (PDN) dose was 10 mg/day in 14 patients, 5 mg/day in two patients and no steroids in one patient. In the remaining 12 patients, moderate initial doses of PDN were administered (mean: 23.7 mg/day, range: 15-40), tapering to 10 mg/day after 1 month. RESULTS: Nephrotic syndrome remission was achieved in 27/29 cases (93.1%) (25 complete, 2 partial). Two patients showed resistance to the prescribed schedule. The first cycle of MF therapy was concluded in 20 patients after a mean (range) of 16.9 months (12-49). Maintenance of remission was observed in 11 of these 20 cases (55%) after a mean follow-up of 32.8 months (12-108). In nine patients with nephrotic syndrome relapse after tapering of MF (MF dependency), the same MF-PDN schedule was restarted, leading again to remission in all nine. The remaining seven MF-sensitive patients are still receiving their first therapeutic cycle. To date, the mean time under therapy in the 27 MF-sensitive patients is 38 months (4-216). Regarding complications, only minor digestive disorders and a slight decrease in blood haemoglobin levels were observed in a few patients. CONCLUSIONS: MF plus reduced doses of PDN is an effective and well-tolerated therapy for adult SD/FR-INS. Though MF dependence is observed, its low toxicity could allow long periods of therapy if it is required to maintain nephrotic syndrome remission.

Religiosidad y cerebro: Las funciones neuropsicológicas en personas creyentes / Religiosity and Brain: Neuropsychological Functions in Believers

Resumen La neuropsicología de la religión permite una apertura científica a la explicación del fenómeno religioso y su impacto en el psiquismo, el presente documento intenta una reflexión que da cuenta de esa estrecha relación e influencia que ejerce la práctica religiosa en la salud mental y en el desarrollo de funciones neuropsicológicas en las personas. Dicha relación, se fortalece con los descubrimientos contemporáneos de la neurociencia cognitiva y la antropobiología.

Abstract Neuropsychology of religion allows a scientific openness to the explanation of the religious phenomenon, and its impact on psychism. This document attempts a re flection, which gives an account of this close relationship, and influence exerted by religious practice on mental health and the development of neuropsychological functions in people. This relationship is strengthened by contemporary discoveries of cognitive neuroscience and anthropology.

Desempeño neuropsicológico ejecutivo de adultos mayores con riesgo cardiovascular: evidencia desde el departamento del Quindío, Colombia / Executive neuropsychological performance of older adults with cardiovascular risk: evidence from Quindío, Colombia

El presente artículo introduce un estudio cuantitativo en el que se compararon los desempeños neuropsicológicos ejecutivos en 20 adultos mayores con antecedentes de riesgo cardiovascular o ACV y sus pares sin dicha condición. Para dicho objetivo se empleó el tamizaje mini mental como criterio de inclusión en la muestra. Igualmente, la investigación indagó la correlación entre el nivel de rendimiento ejecutivo ante la batería neuropsicológica de funciones ejecutivas BANFE 2 y los factores de riesgo cardiovascular. Finalmente, los resultados indicaron que sujetos con historial de ACV presentaron un desempeño más bajo en las funciones ejecutivas orbito frontales y frontal anterior.

The following article introduces a quantitative study in which executive neuropsychological performances were compared in 20 older adults with a history of cardiovascular risk or stroke and their peers without such condition. Mini-mental screening was used as a criterion for inclusion in the sample. The research investigated the correlation between the level of executive performance in the neuropsychological battery of executive functions BANFE 2 and cardiovascular risk factors. Finally, the results indicated that subjects with a history of stroke presented a lower performance in executive functions at the orbitofrontal and frontal lobe.

Filogenia y desarrollo de funciones ejecutivas * / Phylogeny and executive functions development

Resumen El presente documento reflexiona acerca del valor filogenético que tiene para la especie humana el desarrollo de la corteza prefrontal y las funciones ejecutivas. Dicho análisis parte de la revisión de estudios empíricos sobre la génesis de estas en la infancia y la patología de las mismas durante el desarrollo, así como de las evidencias etológicas y paleoantropológicas del proceso de hominización. Igualmente, se discute en el artículo la forma como estas funciones neuropsicológicas le permiten al homo sapiens compensar su carácter biológico de inmadurez y falta de especialidades anatómicas.

Abstract This paper aims to reflect on the phylogenetic value that the development of the pre-frontal cor tex and its executive functions represent for human beings. This analysis is based on the review of empirical studies related to genesis and pathology during childhood, as well as ethological evidence and the process of paleo-anthropological hominization. This paper also analyzes the way these neuropsychological functions allow Homo sapiens to compensate for their biological charac ter of immaturity and lack of anatomical specialties.

Síndrome de McCune-Albright: a propósito de un caso y revisión de la literaturá / McCune-Albright syndrome: a case report and literature review

El síndrome de McCune-Albright (SMA) es una enfermedad rara que produce la mutación del gen codificador de la subunidad alfa de la proteína estimulatoria G de la adenilciclasa que estimula a presentar endocrinopatías múltiples. Esta enfermedad no es hereditaria, sino esporádica y no es transmitida a sus descendientes; causa un amplio espectro de manifestaciones endócrinas y no endócrinas. Es más frecuente en mujeres 3:2 que en hombres. El inicio de estas manifestaciones ocurre usualmente durante la infancia o la niñez. Las manifestaciones clínicas son la triada de: displasia fibrasa ósea, pigmentación irregular en la piel (manchas color café con leche) y pubertad precoz. En cuanto al tratamiento, se debe controlar todo tipo de endocrinopatías con la medicación adecuada así como también en el caso de fracturas patológicas en especial en huesos largos, el empleo de fijación intramedular es la recomendada. Se presenta el caso clínico de una paciente mujer de 6 años de edad con antecedentes de fractura patológica de fémur izquierdo hace 4 meses resuelta con material de osteosintesis (placa DCP) que posteriormente presenta fatiga de material y refractura, además de alteraciones en la pigmentación de la piel, menarquia temprana a los 2 años, por lo que se diagnosticó de Síndrome de Mccune-Albright.