Criteria for melanocytic lesions in LC-OCT.

BACKGROUND: Line-field confocal optical coherence tomography (LC-OCT) is an emerging diagnostic tool with imaging depth reaching ~400 µm and a novel three-dimensional (3D) cube providing cellular resolution. As far as we are aware, there are only a limited number of papers that have reported diagnostic criteria for melanocytic lesions using this technique, and none of them have been multicentric. OBJECTIVES: Our aim was to establish the diagnostic criteria for melanocytic lesions using LC-OCT and identify the most significant architectural and cytologic features associated with malignancy. METHODS: A retrospective evaluation of 80 consecutive melanocytic lesions from a prospective multicentric data set spanning three European centres was conducted. We excluded facial, acral and mucosal lesions from the study. Dermoscopic and LC-OCT images were evaluated by a consensus of four observers. Multivariate logistic regression with backward elimination was employed. RESULTS: The main melanoma diagnostic criteria include detecting >10 pagetoid cells in 3D acquisition, irregular 3D epidermal architecture, disrupted dermoepidermal junction (DEJ) and clefting. Significant risk factors were irregular 3D epidermal architecture, >10 pagetoid cells, dendritic cells at DEJ without underlying inflammation. Novel malignancy criteria in vertical view were DEJ disruption and clefting around atypical melanocyte nests. Exclusive melanoma features were epidermal nests, epidermal consumption, dense dermal nests with atypia. Protective features in the absence of any malignancy indicators were DEJ ring pattern, cobblestone, elongated rete ridges (vertical), well-defined DEJ and wave pattern (vertical). CONCLUSIONS: A series of diagnostic criteria for the identification of melanocytic lesions with LC-OCT have been established. Validation of these criteria in clinical practice through future studies is essential to further establish their utility.

Understanding the anatomy of dermoscopy of melanocytic skin tumours: Correlation in vivo with line-field optical coherence tomography.

BACKGROUND: Early melanoma detection is the main factor affecting prognosis and survival. For that reason, non-invasive technologies have been developed to provide a more accurate diagnosis. Recently, line-field confocal optical coherence tomography (LC-OCT) was developed to provide an in vivo, imaging device, with deep penetration and cellular resolution in three dimensions. Combining the advantages of conventional OCT and reflectance confocal microscopy, this tool seems to be particularly suitable for melanocytic lesions. OBJECTIVES: The objective of this study was to identify and describe the correlation between specific dermoscopic criteria and LC-OCT features in three dimensions associated with melanocytic lesions. METHODS: Dermoscopic and LC-OCT images of 126 melanocytic lesions were acquired in three different centres. The following dermoscopic criteria have been considered: reticular pattern, dots and globules, structureless areas, blue-whitish veil, regression structures, negative network, homogeneous pattern, streaks and blotches. RESULTS: 69 (55%) benign and 57 (45%) malignant lesions were analysed. A regular reticular pattern was found associated in the 75% of the cases with the presence of elongated rete ridges with pigmented cells along the basal layer, while atypical reticular pattern showed an irregular organization of rete ridges with melanocytic hyperplasia, broadened and fused ridges and elongated nests. Both typical and atypical dots and globules were found associated with melanocytic nests in the dermis or at the dermoepidermal junction (DEJ), as well as with keratin cysts/pseudocysts. Grey globules corresponded to the presence of melanin-containing dermal inflammatory cells (melanophages) within the papillae. Structureless brown/black areas correlated with alterations of the DEJ. We observed the same DEJ alterations, but with the presence of dermal melanophages, in 36% of the cases of blue/white/grey structureless areas. A description of each LC-OCT/dermoscopy correlation was made. CONCLUSIONS: LC-OCT permitted for the first time to perform an in vivo, 3D correlation between dermoscopic criteria and pathological-like features of melanocytic lesions.

The efficacy of octreotide LAR as firstline therapy for patients with newly diagnosed acromegaly is independent of tumor extension: predictive factors of tumor and biochemical response.

Surgical outcome of acromegaly depends on the preoperatory tumor size and extension. Somatostatin analogues are also a highly effective treatment for acromegalic patients. Nevertheless, the response of GH-secreting adenomas to primary medical therapy is variable. The aim of the present study was to evaluate the efficacy of octreotide LAR as primary therapy for acromegalic patients as a function of initial tumor extension. We performed a multicentre, prospective, observational and analytical study recruiting 19 "naive" acromegalic patients (5 microadenomas, 10 intrasellar, and 4 extrasellar macroadenomas). All of them were treated with octreotide LAR for 12 months. Basal GH and fasting IGF-I concentrations, and tumor volume were measured at baseline and after 6 and 12 months of treatment. Six patients withdrew the study. The patients who completed the protocol showed a significant reduction of tumor volume (25+/-23%, Wilk's lambda=0.506, F=4.400, p=0.046) independently of tumor extension at study entry (Wilk's lambda=0.826, F=0.452, p=0.769). A shrinkage >25% of baseline tumor volume was achieved in 8 (42%) patients with no differences between tumor extension subgroups. Basal GH levels (76+/-18%) and fasting IGF-I (52+/-31%) decreased throughout the study. Six (46%) patients normalized their IGF-I levels. Octreotide LAR is an effective first-line treatment for a large group of acromegalic patients independent of initial tumor extension.

High-fat versus high-carbohydrate enteral formulae: effect on blood glucose, C-peptide, and ketones in patients with type 2 diabetes treated with insulin or sulfonylurea.

Recently, two commercial enteral formulae for diabetic patients have been made available in Spain: a high-complex-carbohydrate, low-fat formulation (HCF) and a low-carbohydrate formulation (RCF). This study compares the effects of the two enteral nutritional formulae in patients with non-insulin-dependent diabetes mellitus (type 2 diabetes) treated with sulfonylurea or insulin. Fifty-two type 2 diabetes patients were randomly assigned to receive one of the two enteral formulae. Test enteral formula breakfast (250 cc) were consumed at approximately 0900 h after routine medications (insulin or oral agents) had been taken. Venous blood samples were obtained during fasting, before medication, and at 30 and 120 min after the start of the meal. The glycemic response of patients to the HCF was significantly greater than to RCF, but lower than in the sulfonyl type 2 diabetes treated groups. The incremental glucose response was within acceptable levels except in insulin treatment type 2 diabetes patients given HCF. Glucose, insulin, and C-peptide responses were higher in HCF than RCF groups. Two-factor analysis of variance on mean increments of blood glucose and C-peptide from basal levels to 30 min show the type of enteral nutrition as the main factor (P = 0.0010 and P = 0.0005, respectively). The RCF formula supplies 50.0% of energy as fat and 33.3% as carbohydrates, so it may be a ketogenic diet. It was found that both ketone bodies were higher after RCF than after HCF ingestion, but without statistical significance. We conclude that the partial replacement of complex digestible carbohydrates with monounsaturated fatty acids in the enteral formulae for supplementation of oral diet may improve glycemic control in patients with type 2 diabetes. The long-term effects of enteral diets high in monounsaturated fatty acids need further evaluation in patients with type 2 diabetes.

Child-onset growth hormone deficiency in adulthood. Transfer of patients from pediatric to adult endocrinology units.

Treatment with growth hormone (GH) in adult-onset GH deficiency (AO-GHD) reverses its many metabolic alterations, modifying body composition, bone mass, several cardiovascular risk factors, and improving quality of life. In adult patients with a previous diagnosis of child-onset GH deficiency (CO-GHD), the lack of treatment also produces similar alterations, reversed by GH treatment. In patients with multiple pituitary hormone deficiency, the lack of GH is considered definitive, but in isolated GHD, the need for re-evaluation of the deficit is mandatory. The 'gold standard' test is insulin-induced hypoglycemia, after a wash-out period, and the criterion for GH therapy should be a GH (polyclonal-RIA assay) response less than 3 ng/ml. The initial recommended GH dose is lover than in children, and the dosage must be adjusted to maintain IGF-I levels in the normal range. We propose that decisions about patient recruitment, assessment, confirmation or reevaluation, information about new perspectives, disadvantages and benefits of GH therapy, and the beginning of treatment should be made in cooperation by pediatric and adult endocrinologists, so the patient receives all information from both medical teams, before being transferred to the adult endocrinology department.

Adrenal failure due to metastasis both to the hypothalamic-pituitary area and the adrenals.

A 61-year-old white male was admitted to our hospital with a big-cell bronchogenic carcinoma whose first clinical manifestation was diabetes insipidus (DI) secondary to metastasis to the hypothalamic-pituitary area (MHP). In three months, and progressively, he developed anterior pituitary failure, as well as primary adrenal insufficiency (PAI) due to metastasis in both adrenals. Panhypopituitarism or PAI due to both MHP and adrenals has been rarely reported in the literature. A thorough examination of the oncologic patient led us to diagnose hormone insufficiency properly. The absence of reported cases might be due to the fact that the symptoms resulting from hormone insufficiency are veiled by the severe condition of the patients suffering from disseminated cancer.

[Nutritional status and plasma amino acid levels in hemodialysis]. / Estado nutricional y niveles plasmáticos de aminoácidos en hemodiálisis.

The objective of this work is to study the relation between the variations of the plasmatic aminogram, and the nutritional state of the patient with chronic kidney failure on hemodialysis. We studied 79 patients with chronic kidney failure undergoing hemodialysis treatment, with and evolution of 46 +/- 37 months. They were subjected to a dietary questionnaire, and anthropometric study after dialysis (body mass index, triceps skin fold, muscular circumference of the arm), and determination of the levels of serum amino acids after a pre-dialysis nocturnal fast half way through the week, and finally a record is made of the number of times each patient was hospitalized in the 6 months prior to the study. In the amino acids with a pyruvate origin, there is a significant reduction of alanine (p: 0.002), serine (p: 0.004), and methionine (p: 0.001), and a significant increase of glycine, cystathionine, and cystine (p: 0.0001), with the Glycine/Serine coefficient being elevated (p: 0.001). All amino acids with a ketoglutarate origin are increased significantly (p < 0.007), except glutamine which is decreased (p: 0.0009), and arginine which does not show any significant differences. The essential amino acids are decreased in relation to the non-essential ones (p: 0.0001), although if they are compared with the normal values, only threonine is decreased (p: 0.001). Of the rest, histidine, isoleucine (p: 0.0001) and phenylalanine (p: 0.001) are significantly increased. The tyrosine/phenylalanine coefficient is decreased (p: 0.001). The daily ingestion of protein is correlated negatively with alanine, proline, hydroxyproline, and aspartic acid. The anthropometric parameters are correlated positively with the branched amino acids, alanine and proline. Finally, the number of hospital admissions in the last 6 months, is correlated positively with valine, leucine, phenylalanine, and glutamic acid. In conclusion, we consider that the increase of the glycine/serine, phenylalanine/serine and non essential/essential coefficients, is related to alterations of the metabolism, intrinsic to the condition of uremia, while the alterations of the levels of branched amino acids is related to the nutritional condition of the patients.

[Does goiter constitute basically a surgical process?]. / Constituye el bocio un proceso fundamentalmente quirúrgico?

Goiter is usually a clinical manifestation present almost in all the thyroid processes. The over-simple idea of a thyroid tumoration demanding surgical resection is, unfortunately, deeply implanted in many medical and, above all, surgical environments. We tried to estimate the incidence of goiter in a series of thyroid processes and how many of them required surgery. We reviewed the surgical indications in several thyroid entities. In a series of 377 thyroidopathies, goiter was present in 345 (91.5%), 50 of which underwent surgery (12.26% of the total and 14.49 of goiters). Some of the patients were operated in other hospitals without adjusting to the aforementioned criteria and, in theory, just 36 of then should had undergone surgery (9.54% of the total and 10.43% of goiters). In conclusion, surgery has a very secondary role in the treatment of goiter.

Congenital hypothyroidism from complete iodide transport defect: long-term evolution with iodide treatment.

Hypothyroidism from iodide transport deficiency is a rare disease, especially when found in two affected siblings. Treatment with high doses of iodide has been recommended, but no long term results have been reported. Two siblings with congenital hypothyroidism due to total failure to transport iodide have been followed up during twelve and a half years of treatment with oral potassium iodide. Iodine doses varied between 10.3 and 22 mg/day, and serum total iodine concentrations between 100 and 210 micrograms/dl. Total triiodothyronine (T3), thyroxine (T4) and free T4 were in the normal range during the time of study. Basal thyroid stimulating hormones (TSH) and maximum TSH response to thyrotrophin releasing hormone (TRH) were also in the range of normal values. These data along with clinical findings confirmed the potential usefulness of iodine in hypothyroidism due to complete iodide transport defect.

[Metabolic improvement of diabetes mellitus through pamphlets on the norms of self-monitoring control measures]. / Mejoría metabólica de la diabetes mellitus mediante el seguimiento de normas escritas de autocontrol.

OBJECTIVE: To assess whether giving a leaflet containing norms of self-control to diabetics receiving insulin treatment results in a metabolic improvement. The HbA1c was established prior and subsequent to giving out the leaflet. The written norms contained in the leaflet were highlighted from the wider range of instructions obtained from diabetes education. DESIGN: A longitudinal intervention study with no random allocation. SETTING: Hospital care in a specialised Endocrinology clinic. PATIENTS AND OTHER PARTICIPANTS: 122 types 1 and 2 diabetics, treated with various insulin diets, who had received prior diabetes education and carried out blood self-controls. Cases of meta-diabetic syndrome, serious illnesses and those without apparent hypoglycaemia symptoms were excluded. INTERVENTIONS: Giving out of a leaflet with written norms of self-control. MEASUREMENTS AND MAIN RESULTS: The averages, standard deviations and 95% confidence intervals of the basal HbA1c and of those at four-monthly check-ups were calculated. Basal 8.07 (CI 7.75 - 8.39); 4th month 6.88 (CI 6.74 - 7.17); 8th month 6.59 CI 6.29 - 6.90); 12th month 6.60 (CI 6.23 - 6.94); 16th month 6.06 (CI 5.63 - 6.49); 20th month 5.40 (CI 3.04 - 7.75). Averages were compared by the Student T test and all values had p < 0.005 against the basal. CONCLUSIONS: Following the written norms produced a clear metabolic improvement, represented by the significant fall of HbA1c. Therefore, though without ignoring the overall context of treatment and diabetes education, it is proposed that the relationship of the most practical features of insulin dosing to written norms of self-control should be emphasised.

[Flocculation of NPH insulin]. / Floculación de la insulina NPH.

In the past decade, human insulins have been substituting animal insulins, offering the advantage of its lesser antigenic capacity. One of the most clinically important problems with human NPH insulins is its tendency to flocculate. We present four diabetic patients who, after using flocculated human NPH insulin, encountered a deterioration in the metabolic control of their diabetes, and in two of them, there were bouts of diabetic Ketoacidosis "without any other apparent causal factors". Among those causes favoring flocculation are movement during transport, high temperatures, and probably leaving the vial open for an excessively long period of time, as with the extraction of multiple doses. Physicians, educators, diabetics, and their relatives should be informed of this phenomenon. Diabetics, especially those who carry insulin with them, should carefully inspect their vials before each injection to detect signs of flocculation.