Correlation between neuroimaging, neurological phenotype, and functional outcomes in Wilson's disease.

INTRODUCTION: Wilson's disease (WD) is associated with a variety of movement disorders and progressive neurological dysfunction. The aim of this study was to correlate baseline brain magnetic resonance imaging (MRI) features with clinical phenotype and long-term outcomes in chronically treated WD patients. METHODS: Patients were retrospectively selected from an institutional database. Two experienced neuroradiologists reviewed baseline brain MRI. Functional assessment was performed using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) scale, and disease severity was classified using the Global Assessment Scale for Wilson's Disease (GASWD). RESULTS: Of 27 patients selected, 14 were female (51.9%), with a mean (standard deviation [SD]) age at onset of 19.5 (7.1) years. Neurological symptoms developed in 22 patients (81.5%), with hyperkinetic symptoms being the most common (70.4%). Baseline brain MRI showed abnormal findings in 18 cases (66.7%), including T2 hyperintensities in 59.3% and atrophy in 29.6%. After a mean (SD) follow-up of 20.9 (11.0) years, WD patients had a mean score of 19.2 (10.2) on WHODAS 2.0 and 6.4 (5.7) on GASWD. The presence of hyperkinetic symptoms correlated with putaminal T2 hyperintensities (p = 0.003), putaminal T2 hypointensities (p = 0.009), and mesencephalic T2 hyperintensities (p = 0.009). Increased functional disability was associated with brain atrophy (p = 0.007), diffusion abnormalities (p = 0.013), and burden of T2 hyperintensities (p = 0.002). A stepwise regression model identified atrophy as a predictor of increased WHODAS 2.0 (p = 0.023) and GASWD (p = 0.007) scores. CONCLUSIONS: Atrophy and, to a lesser extent, deep T2 hyperintensity are associated with functional disability and disease severity in long-term follow-up of WD patients.

A narrative inquiry into women's experiences of menstruation at the workplace in Namibia.

Background: Menstruation's effects on workplace productivity and its impact on women's careers are rarely discussed in public discourse. This paper presents an analysis of thirteen women's accounts of their menstrual experiences at work. Objectives: The study aimed to understand women's lived experiences of menstruation in the workplace in Namibia and to make recommendations for best practices and policy formulation to help female employees cope with menstruation at work in Namibia. Materials and Methods: The study adopted a qualitative, phenomenological narrative inquiry research design, and thirteen participants working in various institutions and companies in Namibia were selected through a snowball sampling procedure. Individuals who agreed to participate in the study were given a link to a Google document containing reflective questions. Results: Thematic analysis was used to analyze the narratives. The study findings show that most participants experienced various menstrual-related symptoms ranging from unbearable physical pain or discomfort to heavy bleeding and psychological distress. Menstruating women face workplace challenges, such as a lack of emergency sanitary products and unsupportive superiors. Conclusions: Based on the narratives analyzed, we conclude that menstrual-related symptoms affect work productivity. Participants highlighted that they perform better and are considerably more productive on their non-menstrual days. Participants advocated for a shift in policy to allow flexibility to work from home or get menstrual leave when experiencing severe menstrual symptoms. Such a change will go a long way in making the workplace more accommodating to women.

Palliative Care in Advanced Liver Disease: Similar or Different Palliative Care Needs in Patients with a Prospect of Transplantation? Prospective Study from a Portuguese University Hospital and Transplantation Center.

Background and Aims: End-stage liver disease (ESLD) is an important cause of morbidity and mortality, comparable to a large extent to other organ insufficiencies. The need for palliative care (PC) in patients with ESLD is high. In Portugal, in the only identified study, more than 80% of patients hospitalized with ESLD had criteria for PC. No results specified which needs they identified or their transplantation prospect status. Methods: Prospective observational study including 54 ESLD patients who presented to a university hospital and transplantation center, between November 2019 and September 2020. Assessment of their PC needs through the application of NECPAL CCOMS-ICO© and IPOS, considering their transplantation perspective status. Results: Of the 54 patients, 5 (9.3%) were on active waiting list for transplantation and 8 (14.8%) under evaluation. NECPAL CCOMS-ICO© identified 23 patients (n = 42.6%) that would benefit from PC. Assessment of PC needs by clinicians, functional markers and significant comorbidities were the most frequent criteria (47.8%, n = 11). IPOS also revealed a different sort of needs: on average, each patient identified about 9 needs (8.9 ±2.8). Among the symptoms identified, weakness (77.8%), reduced mobility (70.3%), and pain (48.1%) stood out, as well as the psychoemotional symptoms of depression (66.7%) and anxiety (77.8%). There were no significant differences between the subgroups of patients analyzed. Only 4 patients (7.4%) were followed by the PC team. Conclusion: All the ESLD patients included, independently of the group they belonged to, presented with PC needs. No significant differences between the subgroups of patients were identified, confirming that even patients with a transplantation prospect have important needs for PC.

Introdução e objetivos: A doença hepática avançada (DHA) é uma causa importante de morbilidade e mortalidade, comparável em grande medida a outras insuficiências de órgão. A necessidade de cuidados paliativos (CP) em doentes com DHA é elevada. Em Portugal, no único estudo identificado até ao momento, mais de 80% dos doentes hospitalizados com DHA apresentavam critérios para CP. Não foram especificadas que necessidades de CP nem a perspetiva de transplante dos referidos doentes, que com o presente estudo se pretende ajudar a esclarecer. Métodos: Estudo prospectivo observacional incluindo 54 doentes com DHA assistidos num hospital universitário e centro de transplante, entre novembro de 2019 e setembro de 2020. Avaliação das necessidades de CP por meio da aplicação do NECPAL CCOMS-ICO© e IPOS, considerando a sua perspectiva de transplante. Resultados: Dos 54 doentes, cinco (9,3%) estavam em lista de espera ativa para transplante e oito (14,8%) em avaliação. O NECPAL CCOMS-ICO© identificou 23 doentes (n = 42,6%) que beneficiariam de CP. A avaliação das necessidades de CP por médicos, os marcadores funcionais e as comorbidades significativas foram os critérios mais frequentes (47,8%, n = 11). O IPOS também revelou diversas necessidades de CP: em média, cada doente identificou cerca de 9 necessidades (8,9 + −2,8). Entre os sintomas identificados, destacaram-se a fraqueza (77,8%), a mobilidade reduzida (70,3%) e a dor (48,1%), bem como os sintomas psicoemocionais de depressão (66,7%) e ansiedade (77,8%). Não houve diferenças significativas entre os subgrupos de doentes analisados. Apenas 4 doentes (7,4%) foram acompanhados pela equipa intra-hospitalar de CP. Conclusão: Todos os doentes com DHA incluídos, independentemente do grupo a que pertenciam, apresentaram necessidades de CP. Não foram identificadas diferenças significativas entre os subgrupos de doentes, confirmando que mesmo os doentes com perspectiva de transplante têm importantes necessidades de CP.

Trace Element Imbalances in Acquired Hepatocerebral Degeneration and Changes after Liver Transplant.

Brain manganese (Mn) accumulation is a key feature in patients with acquired hepatocerebral degeneration (AHD). The role of trace elements other than Mn in AHD needs to be clarified. In this study, using inductively coupled plasma mass spectrometry, we aimed to evaluate blood levels of trace elements in patients with AHD before and after liver transplantation (LT). Trace element levels in the AHD group were also compared with those of healthy controls (blood donors, n = 51). Fifty-one AHD patients were included in the study (mean age: 59.2 ± 10.6 years; men: 72.5%). AHD patients had higher levels of Mn, Li, B, Ni, As, Sr, Mo, Cd, Sb, Tl and Pb and a higher Cu/Se ratio, and lower levels of Se and Rb. Six patients (two women; mean age 55 ± 8.7 years) underwent LT, and there was an improvement in neurological symptoms, a significant increase in the Zn, Se and Sr levels, and a decrease in the Cu/Zn and Cu/Se ratios. In summary, several trace element imbalances were identified in AHD patients. Liver transplantation resulted in the improvement of neurological manifestations and the oxidant/inflammatory status. It is possible that observed changes in trace element levels may play a role in the pathophysiology and symptomatology of AHD.

Prognostic Impact of Type 2 Diabetes in Metastatic Colorectal Cancer.

Background Diabetes mellitus (DM) is a prognostic factor for some malignancies, but its clinical implications in metastatic colorectal cancer (mCRC) patients are less clear. Therefore, we conducted a retrospective study to evaluate the impact of pre-existing type 2 diabetes mellitus (T2DM) on the survival outcomes of patients with newly diagnosed mCRC. Methodology We retrospectively included patients with newly diagnosed mCRC between January 2017 and June 2021 and with pre-existing T2DM. Data on the characteristics of patients, clinicopathological features, and drug exposure were collected from the electronic medical records. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS) and treatment-related adverse events (TRAEs). Results Among 187 mCRC patients, 54 (28.8%) had T2DM. The median follow-up was 25 months. We observed 150 OS events and 168 PFS events. Diabetes significantly and negatively impacted PFS and OS. The median for PFS (mPFS) was eight and 16 months for T2DM and no T2DM patients, respectively (p < 0.0001; log-rank test). The median overall survival (mOS) was 15 and 29 months for T2DM and no T2DM patients, respectively (p < 0.0001; log-rank test). Patients with diabetes were more often overweight or obese (59.3% vs. 24.8%; p < 0.01) and had a poorer performance status (53.7% vs. 21.1% with Eastern Cooperative Oncology Group Performance Status 1; p < 0.01). Additionally, T2DM patients had more high-risk pathological features, including G3 grading tumors (27.7% vs. 12.0%; p = 0.01), lymph node involvement (p < 0.01), BRAF-mutated (35.1% vs. 6.8%; p < 0.01), and right-sided CRC (63.0% vs. 30.1%; p < 0.01). We found no statistically significant differences in TRAEs. Nevertheless, a significantly higher rate of grade 2-4 peripheral neuropathy (22.2% vs. 5.3%; p < 0.01) was reported in T2DM patients. Conclusions T2DM is a negative prognostic factor for survival in mCRC. The paper provides empirical evidence in favor of the joint control of both pathologies. Further research is needed to establish the robustness of our results.

Pembrolizumab-Induced Autoimmune Grade 4 Neutropenia in a Patient With Advanced Bladder Cancer: A Case Report.

Neutropenia is amongst the rare, but potentially life-threatening complications of immune checkpoint inhibitors (ICI). Awareness about this dangerous toxicity and its adequate treatment since early detection is of utmost importance. Unfortunately, there are no therapeutical guidelines to deal with neutropenia specifically. The best alternative is informed extrapolations based on reported neutropenia cases and established guidelines for other immune-related adverse events. We report a case of pembrolizumab-related grade 4 neutropenia in a patient with metastatic bladder cancer. She was successfully treated with immunosuppressive and supportive measures. Further studies are required to understand the range of immune-related adverse events and to improve their management.

Brain MRI in the Decision for Liver Transplantation in Pediatric Neurological Wilson's Disease.

Background: Neurological Wilson's disease (WD) presentation in the pediatric population is rare, and liver transplantation (LT) in these patients remains controversial. The aim of the present study was to assess the role of brain magnetic resonance imaging (MRI) in predicting reversion of brain lesions and neurological outcomes in pediatric WD patients after LT. Methods: Patients with confirmed WD (Leipzig score ≥4), disease onset in pediatric age (<18 years), neurological involvement, and submitted to LT were selected. Clinical records and pre- and post-LT brain MRI were evaluated. Results: Six patients met the pre-defined inclusion criteria, one of whom died shortly after LT and was excluded. The indication for LT was end-stage liver disease in two patients and neurological worsening despite optimized treatment in three patients. After LT, the neurological picture progressively improved in all patients. Pre-LT brain MRI showed T1-weighted hyperintensities in four patients, which quickly resolved afterward. T2-weighted hyperintensities were observed in four patients before LT, completely resolving in one patient, stabilizing in two, and improving in one after LT. A direct correlation could not be found between clinical and neuroradiological improvement. Progressive clinical improvement was observed even in patients with irreversible brain MRI changes. Conversely, some patients with normal MRI had only slight neurological improvement. Conclusions: The pattern of T2-weighted hyperintensities after LT was unpredictable and did not correlate with neurological outcomes, suggesting that these changes may not entail irreversible clinical damage. Therefore, brain MRI does not seem to have prognostic value for assessing clinical response to LT.

Impact of Human Epidermal Growth Factor Receptor 2 (HER2) Low Status in Response to Neoadjuvant Chemotherapy in Early Breast Cancer.

Introduction In clinical practice, there is a binary distinction between human epidermal growth factor receptor 2 (HER2)-positive and HER2-negative (HER2-) breast cancer (BC). However, within HER2- disease, there is significant heterogeneity. Particularly, HER2- tumors that express some level of HER2 by immunohistochemistry (IHC) score 1+ or 2+/in situ hybridization (ISH) non-amplified are currently defined as HER2-low. This subgroup has shown distinct biological features compared to HER2-zero (HER2-0) BC and additionally novel antibody-drug conjugate therapies have demonstrated a potential and promising activity in HER2-low BC population. This study aims to evaluate the impact of HER2-low status in response to neoadjuvant chemotherapy (NACT) in HER2- BC being HER2-low and HER2-0 status. Materials and methods In a single institution, we retrospectively reviewed clinical and pathological data of HER2 early-stage BC patients treated with NACT following definitive surgery from January 2015 to December 2020. Tumors with HER2 IHC 0 were classified as HER2-0 and IHC score 1+ and 2+/ISH non-amplified as HER2-low. The primary objective was to evaluate the rate of pathological complete response (pCR) using the definition of ypT0/Tis ypN0 according to HER2-low and HER2-0 subgroups. Secondary objectives were to evaluate biological features between the two subgroups, disease-free survival (DFS), and overall survival (OS). Pearson chi-square, Fisher's exact, and Mann-Whitney tests were performed. The Kaplan-Meier method was used to plot DFS and OS curves. A p-value of <0.05 was considered statistically significant. Results A total of 72 patients with HER2 BC were included with a median age at diagnosis of 52.5 years and a median follow-up time of 35.5 months. Of patients, 56.9% had HER2-low disease and 43.1% had HER2-0 disease. Significant differences between the two subgroups were detected regarding hormonal receptor status and proliferation grade (Ki67). In the HER2-low subgroup, 70% of tumors were luminal-like and 64.5% of HER2-0 patients had triple-negative BC (p = 0.03). There were statistically significant differences regarding estrogen (p = 0.00) and progesterone (p = 0.02) receptors. The median Ki67 rate was higher in the HER2-0 subset (mean rank = 43.9) compared to HER2-low (mean rank = 30.9) and this difference was statistically significant (p = 0.00). HER2-low patients presented more stage III tumors (65.9%) and HER2-0 patients were mainly stage II (61.3%), and this was statistically relevant (p = 0.03). The prevalence of other clinical and pathological features was comparable between both groups. HER2-low subgroup achieved lower pCR rates (14.6% vs. 29.0%) but this difference was not statistically significant (p = 0.15). Similarly, there was no difference between the two subgroups regarding DFS (p = 0.97) and OS (p = 0.35), although the data were immature. Conclusion As in prior studies, this study did not support a significant impact of HER2-low status on response to NACT in HER2- patients with early-stage BC. HER2-low patients had a lower pCR, which may suggest a worse response to classic chemotherapy regimen and may have clinical implications that should be further exploited. The prevalence of hormonal receptors in HER2-low tumors was consistent with previous data in the literature. Although retrospective, the data suggest that HER2-low tumors should be regarded as a distinct biological subtype and more research is warranted.

Cutaneous and Cerebral Metastases From Primary Peritoneal Clear Cell Carcinoma.

Peritoneal tumors are very uncommon and among them, primary peritoneal clear cell carcinoma is extremely rare and often misdiagnosed as others subtypes. There are only 13 cases of primary peritoneal clear cell carcinoma previously reported in the literature and there are no reports about cutaneous metastasis in this setting and only brain metastases were described to be associated with other primary peritoneal carcinoma subtypes. More information about this topic is needed and so we are presenting a new case of primary peritoneal clear cell carcinoma with cutaneous and cerebral metastases in a 34-year-old female.

Systemic inflammation as a risk factor for portal vein thrombosis in cirrhosis: a prospective longitudinal study.

BACKGROUND AND AIMS: Various risk factors for portal vein thrombosis (PVT) development in patients with cirrhosis have been identified, but the role of systemic inflammatory reaction is unknown. The study aims to assess the association between markers of systemic inflammation and PVT in cirrhosis. METHODS: Between January 2014 and October 2015, 107 outpatients with cirrhosis and no PVT were recruited, and followed till February 2017. White blood cell count, serum concentrations of high-sensitive C-reactive protein, ferritin, tumor necrosis factor-alpha and interleukin-6 (IL-6) were evaluated at baseline and every 3 or 6 months till PVT diagnosis or end of follow-up. RESULTS: Median age, model for end-stage liver disease (MELD) score and follow-up period of the studied population was 55 years (IQR 46-62 years), 9.6 points (IQR 7.5-12 points) and 19 months (12-24 months), respectively. PVT developed in 10.3% of the patients. Lymphocyte count below 1.2 ´ 109/L [hazard ratio, 6.04; 95% confidence interval (CI), 1.29-28.2; P = 0.022], IL-6 above 5.5 pg/mL (hazard ratio, 5.64; 95% CI, 1.21-26.33; P = 0.028) and neutrophil-to-lymphocyte ratio (hazard ratio, 1.46; 95% CI, 1.04-2.04; P = 0.028) were associated with a higher risk of PVT development. IL-6 and lymphopenia remained associated with subsequent PVT development after adjustment for nonselective beta-blockers, spleen size, portosystemic collaterals, oesophageal varices (grade ≥2) and ascites, but also with alcohol as the cause for cirrhosis and MELD ≥13. CONCLUSION: In patients with cirrhosis, markers of systemic inflammation IL-6 and lymphopenia are predictive of PVT independently of markers of portal hypertension. These results draw our attention on a factor so far overlooked in the pathogenesis of PVT.

Palliative Care in End-Stage Liver Disease Patients Awaiting Liver Transplantation: Review.

INTRODUCTION: End-stage liver disease (ESLD) is the advanced phase of most liver diseases. The cure is liver transplantation (LT), only available for a minority of patients. This review summarizes the evidence regarding palliative care (PC) in ESLD patients awaiting LT. METHODS: Review of the literature available in Medline, Scopus and Web of Knowledge, with keywords ESLD and PC. RESULTS: Fifteen of the 230 articles reviewed met the inclusion criteria. Ten main themes were addressed: symptom burden; perspectives of life-sustaining treatment and comfort for patients, families and health professionals; goals of care discussions; patient and family needs; quality of life; PC and survival; referral to PC, barriers and opportunities; integration of PC; outpatient care and cost-effectiveness analysis. The referral of patients to PC was only evaluated in a few studies, all of which reported low referral rates. Better knowledge of how PC professionals can support other professionals was considered important, and also better ways to integrate PC were considered essential. CONCLUSION: ESLD patients awaiting LT have a significant need for PC and, despite the insufficient response, were reported to benefit from this type of care. Future research is essential to determine the means to overcome barriers and better integrate PC for ESLD patients awaiting LT.

INTRODUÇÃO: A doença hepática avançada (DHA) corresponde à fase mais avançada das doenças hepáticas. O transplante hepático (TH) é o tratamento curativo, disponível apenas para uma minoria de doentes. Esta revisão sumariza a evidência sobre cuidados paliativos (CP) em doentes com DHA que aguardam TH. MÉTODOS: Revisão da literatura existente na Medline, Scopus e Web of Knowledge. Palavras chave pesquisadas CP e DHA. RESULTADOS: Quinze dos 230 artigos encontrados cumpriram critérios de inclusão. Dez temáticas foram abordadas: carga sintomática; discussão de objectivos de cuidados; perspectivas sobre tratamentos de suporte artificial e conforto; necessidades do doente e família; qualidade de vida; CP e impacto no prognóstico; referenciação para CP, barreiras e oportunidades; integração dos CP; cuidados de ambulatório e análises de custo-benefício. Poucos estudos avaliaram a referenciação para CP, todos com baixas taxas. Mais conhecimento e formação dos profissionais que acompanham doentes com DHA parece ser necessário, bem como, melhor articulação entre os diferentes intervenientes. CONCLUSÃO: Doentes com DHA que aguardam TH apresentam importantes necessidades de CP. Apesar da insuficiente resposta a este nível, parecem beneficiar deste tipo de cuidados. Estudos futuros que clarifiquem como ultrapassar as barreiras e a melhor integração dos CP nos doentes que aguardam TH são essenciais.

Endocrine therapy for the treatment of leptomeningeal carcinomatosis in luminal breast cancer: a comprehensive review.

Leptomeningeal disease (LMD) represents a devastating complication of advanced breast cancer (ABC), with survival of <5 months with multimodal treatment. The role of endocrine therapy (ET), due to its favorable toxicity profile and first-line indication in luminal ABC, appears promising in the setting of LMD, where symptom stabilization and quality-of-life preservation are the main goals; however, evidenced-based data are lacking. We conducted a thorough review of published evidence, aiming to investigate the role of ET in LMD treatment in luminal ABC. Twenty-one of 342 articles, evaluating 1302 patients, met inclusion criteria. ET use was rarely reported. New targeted agents show CNS activity. Research is lacking on the role of ET and targeted agents in BC-LMD treatment.

The effect of pain management group on chronic pain and pain related co-morbidities and symptoms. A stepped-wedge cluster randomized controlled trial. A study protocol.

INTRODUCTION: In primary care settings, pain-management group therapy is a tool potentially cost-effective but very much underused. METHODS: Our purpose here is to provide useful scientific information on the effect of pain-management group participation on chronic pain and pain-related co-morbidities and symptoms, as well as practical information for primary and occupational health services to initiate pain-management group activity.This study will be carried out at primary care Occupational Health Helsinki (Helsinki city employees' occupational health services), with the Finnish Institute of Occupational Health as the research partner.This is a stepped-wedge cluster randomized controlled trial among both male and female municipal employees aged 18 to 65, all of whom had visited an occupational doctor, nurse, psychologist, or physiotherapist because of any chronic pain unrelated to malignant disease. An additional inclusion criterion is work disability risk being elevated, based on a short screening questionnaire (modified Örebro questionnaire). Each participant and each interviewer will be blinded at randomization.Three groups, 10 subjects in each, begin directly after recruitment with 6 weekly 2-h meetings and a follow-up meeting 6 months later. Three waiting-list groups begin 4 months later. Subjects complete self-administered questionnaires before and after the sixth meetings, also 6 months later. Primary outcomes are pain intensity, current work ability, pain self-efficacy, fear-avoidance beliefs, chronic pain acceptance, depressive symptoms, sleep problems, sickness absence days, and number of occupational health care contacts from OH's medical records. RESULTS: We will publish our results in a peer-reviewed scientific journals.

The effect of pain management group on chronic pain and pain related co-morbidities and symptoms. A stepped-wedge cluster randomized controlled trial. A study protocol.

INTRODUCTION: In primary care settings, pain-management group therapy is a tool potentially cost-effective but very much underused. METHODS: Our purpose here is to provide useful scientific information on the effect of pain-management group participation on chronic pain and pain-related co-morbidities and symptoms, as well as practical information for primary and occupational health services to initiate pain-management group activity.This study will be carried out at primary care Occupational Health Helsinki (Helsinki city employees' occupational health services), with the Finnish Institute of Occupational Health as the research partner.This is a stepped-wedge cluster randomized controlled trial among both male and female municipal employees aged 18 to 65, all of whom had visited an occupational doctor, nurse, psychologist, or physiotherapist because of any chronic pain unrelated to malignant disease. An additional inclusion criterion is work disability risk being elevated, based on a short screening questionnaire (modified Örebro questionnaire). Each participant and each interviewer will be blinded at randomization. Three groups, 10 subjects in each, begin directly after recruitment with 6 weekly 2-h meetings and a follow-up meeting 6 months later. Three waiting-list groups begin 4 months later. Subjects complete self-administered questionnaires before and after the sixth meetings, also 6 months later. Primary outcomes are pain intensity, current work ability, pain self-efficacy, fear-avoidance beliefs, chronic pain acceptance, depressive symptoms, sleep problems, sickness absence days, and number of occupational health care contacts from OH's medical records. RESULTS: We will publish our results in a peer-reviewed scientific journals.

Sweet's Syndrome Induced by Aromatase Inhibitor in the Treatment of Early Breast Cancer.

BACKGROUND: Breast cancer is the most commonly diagnosed cancer in women, mainly at an early stage, allowing treatment with curative intent. Aromatase inhibitors are widely used in the adjuvant treatment of oestrogen receptor-positive breast cancer, mainly in postmenopausal women. The most frequent adverse events associated with these therapies are musculoskeletal symptoms and an increased risk of bone fractures. Cutaneous adverse events have been rarely described. Sweet's syndrome can present as an idiopathic disorder in addition to being malignancy-associated or drug-induced. CASE PRESENTATION: We report the case of a 69-year old woman, diagnosed with early stage breast cancer, who underwent breast-conserving surgery, followed by adjuvant radio and endocrine treatment with letrozole 2.5 mg daily, for a foreseeable duration of 5 years. Three months after starting letrozole, she presented with sudden fever and exuberant and painful erythematous skin papules and plaques on her upper body. After a full work-up and exclusion of other potential causes, a skin biopsy confirmed the presence of dermal oedema and a diffuse neutrophilic infiltrate, suggesting Sweet's syndrome. After discontinuation of letrozole and treatment with corticosteroids, the patient fully recovered. She resumed adjuvant treatment with tamoxifen, without symptom recurrence. CONCLUSIONS: Sweet's syndrome is a rare condition and an association with aromatase inhibitors has not been previously reported. Although its occurrence has already been observed in the onset of malignancies such as breast cancer, aromatase inhibitors must be added to the list of potential causes of drug-induced Sweet's syndrome. LEARNING POINTS: Aromatase inhibitors are widely used in the treatment of breast cancer and, though infrequent, it is important to recognize possible cutaneous adverse events.Sweet's syndrome is a rare but troublesome condition. Prompt recognition and management are crucial to alleviate symptoms.Drug-induced Sweet's syndrome associated with aromatase inhibitors has not been previously reported and should be considered when evaluating treatment toxicities.

Budd-Chiari Syndrome and Acute Liver Failure: An Uncommon Presentation of Acute Myeloid Leukaemia.

Acute liver failure (ALF) is a rare entity, particularly in the context of Budd-Chiari syndrome (BCS). BCS is an uncommon disorder with multiple risk factors, most commonly myeloproliferative disorders. In BCS, active search and exclusion of underlying malignancy is mandatory, particularly in the context of ALF, as it may contraindicate liver transplantation (LT). We present the case of a healthy 29-year-old male, without known risk factors for liver disease, who presented to the emergency department with abdominal pain, ascites, and jaundice. BCS with consequent severe acute liver injury with rapid progression to ALF was diagnosed. The patient was listed for LT. The study of peripheral blood finally revealed myeloid blasts, and flow cytometry showed a population of blast cells with abnormal immunophenotypic profile (CD33+ and myeloperoxidase, MPO+). The bone marrow biopsy showed morphological and immunophenotypic aspects of acute myeloid leukaemia (AML) FAB M1. This diagnosis was considered a formal contraindication to LT, so the patient was delisted. ALF contraindicated rescue chemotherapy and AML contraindicated LT. The patient died 48 h after ICU admission. The search for underlying neoplasia is mandatory in the context of BCS, moreover with associated ALF, as it may limit lifesaving treatments and interventions to supportive and palliative care.

A falência hepática aguda (FHA) é uma entidade rara, particularmente no contexto da Síndrome de Budd-Chiari (SBC). A SBC é uma doença incomum com múltiplos fatores de risco, principalmente as doenças mieloproliferativas. Na SBC, a procura ativa e exclusão de malignidade subjacente é obrigatória, particularmente no contexto de FHA, já que pode contraindicar o transplante hepático (TH). Apresentamos o caso de um homem de 29 anos saudável, sem fatores de risco conhecidos para doença hepática que se apresentou no serviço de urgência com dor abdominal, ascite e icterícia. A SBC associada a lesão hepática severa com rápida progressão para FHA foi diagnosticada e o doente colocado em lista para TH. O estudo do sangue periférico finalmente revelou a presença de blastos mieloides e a citometria de fluxo a presença de uma população de blastos com perfil imunofenotípico anormal (CD33 + e mieloperoxidase (MPO) +). A biópsia da medula óssea mostrou aspetos morfológicos e imunofenotípicos de leucemia mieloide aguda (LMA) FAB M1. Este diagnóstico foi considerado uma contraindicação formal para o TH, pelo que o doente foi retirado de lista. Pela FHA a quimioterapia de resgate estava também contraindicada. O doente faleceu 48 horas após a admissão na UCI. O despiste de neoplasia subjacente é obrigatório no contexto de SBC, ainda mais com FHA, pois pode limitar o tratamento lifesaving a cuidados de suporte e paliativos.

Metastatic extramammary paget disease, a remarkable clinical case and a brief review of a rare disease.

Extramammary Paget Disease (EMPD) is an often-misdiagnosed rare disorder, whose cause remains unknown. Diagnosis is confirmed by skin biopsy. Primary treatment for EMPD is surgery. Recurrence is common in the first two years and prognosis is good if the disease is localized and there is no underlying associated cancer. Patients with invasive and metastatic EMPD are uncommon and exhibit a poor prognosis, even when there is good response to a first chemotherapy line. Multiple chemotherapeutic regimens, with varying levels of success, have been attempted, but standard of care is not established. The central nervous system seems to be a common metastatic site with better survival than visceral metastasis.We report a case of metastatic EMPD that addresses the difficulties associated with the treatment of this rare disease, that has no current guidelines.

Nonselective beta-blockers and the risk of portal vein thrombosis in patients with cirrhosis: results of a prospective longitudinal study.

BACKGROUND: Nonmalignant portal vein thrombosis is a significant event in the course of cirrhosis that can contraindicate liver transplantation and even impact survival after the surgical procedure. Risk factors are not completely known or validated and are still debated. AIM: To identify in patients with cirrhosis the risk factors for portal vein thrombosis that are assessable in clinical practice. METHODS: Between January 2014 and February 2017, 108 outpatients with cirrhosis and no portal vein thrombosis (78% Child A) were enrolled. Doppler ultrasound was performed every 3 or 6 months, for a median follow up of 19 months. RESULTS: Portal vein thrombosis developed in 11 patients. Nonselective beta-blockade (hazard ratio [HR] 10.56; 95% confidence interval [CI]: 1.35-82.73; P = 0.025), and medium or large-sized oesophageal varices (HR 5.67; 95% CI: 1.49-21.63; P = 0.011) at baseline were associated with portal vein thrombosis development. Although heart rate (P < 0.001) and portal blood flow velocity at baseline (P = 0.005) were significantly reduced by nonselective beta-blockers, they were not related to portal vein thrombosis development. CONCLUSIONS: Our findings confirm an association between portal vein thrombosis development and oesophageal varices at baseline, but suggest that the association could be explained by exposure to nonselective beta-blockers, independently from effects on heart rate and portal blood flow velocity. The mechanisms that explain portal vein thrombosis development in patients on nonselective beta-blockers require elucidation in order to optimise targeting of nonselective beta-blockade in patients with cirrhosis.