Foot ulceration is one of the most debilitating complications associated with diabetes, but its cause remains poorly understood. Several studies have been undertaken to understand healing kinetics or find possible therapies to enhance healing. However, few studies have been directed at understanding the immunological alterations that could influence wound healing in diabetes. In this study, we analysed the T-cell receptor (TCR) repertoire diversity in TCR-αβ T cells. We also analysed the distribution and phenotype of T cells obtained from the peripheral blood of healthy controls and diabetic individuals with or without foot ulcers. Our results showed that diabetic individuals, especially those with foot ulcers, have a significantly lower naive T-cell number and a poorer TCR-Vβ repertoire diversity. We also showed that the reduced TCR-Vβ repertoire diversity in diabetic individuals was mainly owing to the accumulation of effector T cells, the major source of tumour necrosis factor-α production, which was even more pronounced in patients with acute foot ulceration. Moreover, the expression of several inflammatory chemokine receptors was significantly reduced in diabetic patients. In conclusion, effector T-cell accumulation and TCR repertoire diversity reduction appear to precede the development of foot ulcers. This finding may open new immunological therapeutic possibilities and provide a new prognostic tool in diabetic wound care.

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Summary Pituitary metastasis (PM) can be the initial presentation of an otherwise unknown malignancy. As PM has no clinical or radiological pathognomonic features, diagnosis is challenging. The authors describe the case of a symptomatic PM that revealed a primary lung adenocarcinoma. A 62-year-old woman with multiple sclerosis and no history of malignancy, incidentally presented with a diffusely enlarged and homogeneously enhancing pituitary gland associated with stalk enlargement. Clinical and biochemical evaluation revealed anterior hypopituitarism and diabetes insipidus. Hypophysitis was considered the most likely diagnosis. However, rapid visual deterioration and pituitary growth raised the suspicion of metastatic involvement. A search for systemic malignancy was performed, and CT revealed a lung mass, which proved to be a lung adenocarcinoma. Accordingly, the patient was started on immunotherapy. Resection of the pituitary lesion was performed, and histopathology analysis revealed metastatic lung adenocarcinoma. Following surgery, the patient underwent radiotherapy. More than 2 years after PM detection, the patient shows a clinically relevant response to antineoplastic therapy and no evidence of PM recurrence. Learning points Although rare, metastatic involvement of the pituitary gland has been reported with increasing frequency during the last decades. Pituitary metastasis can be the initial presentation of an otherwise unknown malignancy and should be considered in the differential diagnosis of pituitary lesions, irrespective of a history of malignancy. The sudden onset and rapid progression of visual or endocrine dysfunction from a pituitary lesion should strongly raise the suspicion of metastatic disease. MRI features of pituitary metastasis can overlap with those of other pituitary lesions, including hypophysitis; however, rapid pituitary growth is highly suggestive of metastatic disease. Survival after pituitary metastasis detection has improved over time, encouraging individualized interventions directed to metastasis to improve quality of life and increase survival.

Purpose To assess the accuracy of bilateral inferior petrosal sinus sampling both in the differential diagnosis of adrenocorticotrophic hormone dependent Cushing’s syndrome and predicting the localization on the pituitary. Methods The authors evaluated all patients that undergone bilateral inferior petrosal sinus sampling in a tertiary centre, between January 1995 and March 2018. The probable diagnosis of Cushing’s disease was made when the basal central/peripheral gradient was>2 and/or>3 after stimulation with corticotrophin releasing hormone. The localization was suggested when the inter-sinus gradient was>1.4. The results obtained were compared with the post operatory results: compatible histology and positive immunohistochemistry to adrenocorticotrophic hormone and/or the presence of criteria of cure. Sensitivity, specificity and predictive positive value were calculated. Results A total of 49 patients were evaluated (75.5% female; mean age 45.4±16.3 years old). Bilateral inferior petrosal sinus sampling was compatible with Cushing’s disease in 27 out of 28 confirmed cases in histology or by criteria of cure, and was compatible with ectopic secretion in the 2 cases confirmed as ectopic secretion of adrenocorticotrophic hormone (sensitivity 96.4%; specificity 100%). The lateralization calculated was concordant with the results after surgery in 17 out of 27 patients with Cushing’s disease – predictive positive value of 63%. Magnetic resonance had a higher predictive value to lateralization – 70.0%. Conclusions Bilateral inferior petrosal sinus sampling is a safe and reliable procedure to diagnose Cushing’s disease, with great sensitivity and specificity. Nevertheless, the capacity of this procedure to lateralize the lesion inside the pituitary is limited.

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Recebido a 2 de junho de 2014; aceite a 29 de agosto de 2014 Disponível na Internet a 11 de outubro de 2014 PALAVRAS-CHAVEÚlcera do pé diabético; Epidemiologia; Neuropatia periférica; Doença arterial periférica; Consulta multidisciplinar ResumoIntrodução: A diabetes mellitus é responsável por 70% das amputações não traumáticas do membro inferior e 85% destas são precipitadas por úlceras. Objetivo ---caracterização epidemiológica e resultado da intervenção dos utentes da consulta multidisciplinar do pé diabético. Materiais e métodos: Estudo observacional retrospetivo das primeiras consultas realizadas no âmbito da consulta multidisciplinar do pé diabético, durante um semestre. Revisão do processo clínico e avaliação das características epidemiológicas, investigação clínica realizada, meios complementares de diagnóstico e o resultado final (cicatrização da lesão, amputação major, não cicatrização em um ano ou morte). Resultados: Realizaram-se 361 primeiras consultas do pé diabético no período em estudo, 82,3% por ulceração (31,3% neuropáticos e 68,7% neuroisquémicos). Dos doentes seguidos, 78% obtiveram cicatrização das lesões (com ou sem amputação minor), 7,7% não obtiveram cicatrização da lesão após um ano de seguimento, 10,1% foram submetidos à amputação major e 4,2% faleceram durante o seguimento. Os doentes com doença arterial periférica apresentaram menor probabilidade de cicatrização (70,6 vs. 89,4%, p = 0,004) e risco aumentado de amputação major (15,7 vs. 1,5%, p = 0,003). A nefropatia diminuiu a probabilidade de cicatrização (50 vs. 82,6%, p = 0,008) e aumentou o risco de amputação major (29,1 vs. 6,9%, p = 0,008). Os doentes com dependência de terceiros apresentaram maior risco de amputação major (22,9 vs. 6,8%, p = 0,008). * Autor para correspondência. Correio eletrónico: vitormiguelferreira@hotmail.com (V. Ferreira).

Background. The incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) has been increasing in the last five decades, but there is no large-scale data regarding these tumours in Portugal. We conducted a cross-sectional, multicentric study in main Portuguese centers to evaluate the clinical, pathological, and therapeutic profile of GEP-NENs. Methods. From November, 2012, to July, 2014, data from 293 patients diagnosed with GEP-NENs from 15 centers in Portugal was collected and registered in an online electronic platform. Results. Median age at diagnosis was 56.5 (range: 15-87) years with a preponderance of females (54.6%). The most frequent primary sites were the pancreas (31.1%), jejunum-ileum (24.2%), stomach (13.7%), and rectum (8.5%). Data regarding hormonal status was not available in most patients (82.3%). Stratified by the tumour grade (WHO 2010 classification), we observed 64.0% of NET G1, 24.7% of NET G2, and 11.3% of NEC. Poorly differentiated tumours occurred mainly in older patients (p=0.017), were larger (p<0.001), and presented more vascular (p=0.004) and lymphatic (p=0.001) invasion. At the time of diagnosis, 44.4% of GEP-NENs presented metastatic disease. Surgery (79.6%) and somatostatin analogues (30.7%) were the most frequently used therapies of GEP-NENs with reported grading. Conclusion. In general, Portuguese patients with GEP-NENs presented similar characteristics to other populations described in the literature. This cross-sectional study represents the first step to establish a national database of GEP-NENs that may aid in understanding the clinical and epidemiological features of these tumours in Portugal.

This study reports on the case of an elderly patient, with diabetes, and a bullous wound on the left big toe that led to an amputation of the first and second left toes. The amputation was because of deep injury as it was not able to heal with a conventional treatment. After completing the normal treatment and the removal of a bacterial infection in the lesion, the patient underwent a treatment that was based on a hydrogel gel (0.9% saline solution) and hyperbaric oxygen therapy (HBOT). After 60 sessions of the therapy, almost complete closure of the wound was observed. There were no reports of discomfort or infection during the treatment. After seven months of treatment almost complete healing was observed with no infection. This treatment appears to be effective and should be recommended for the treatment of DFUs.