Anti-N-Methyl-D-Aspartate Receptor Encephalitis, A Diagnosis Not To Miss.

Anti-N-methyl-D-aspartate receptor (Anti-NMDAR) encephalitis is a rare autoimmune disease, characterized by the presence of neuropsychiatric symptoms. It is sometimes mistaken for a psychiatric disorder and other times not considered in the differential diagnosis of an encephalitic process. Correct identification of this disease and prompt treatment are key for optimal recovery, which might take weeks to months. Many patients manifest severe symptoms, with depressed level of consciousness, breathing dysfunction and dysautonomia requiring admission to the Intensive Care Unit (ICU). We report the case a young male patient with anti-NMDA encephalitis who presented typical neuropsychiatric symptoms. Despite being diagnosed and treated in a timely manner, he did not respond well to first-line immunotherapy and was admitted to the ICU with neurological, respiratory, and cardiovascular dysfunction. This resulted in prolonged hospital admission and many infectious complications. Despite the severity of the disease, the patient managed to recover in the months following discharge from hospital. LEARNING POINTS: Anti-NMDAR encephalitis is a clinical entity described relatively recently, typically manifesting as a neuropsychiatric disorder and which should be in the differential diagnosis of any case of encephalitis, especially in young patients.Important prognostic factors for anti-NMDA encephalitis are lack of clinical improvement within the first four weeks of treatment and need for admission to the ICU.Anti-NMDAR encephalitis is a severe disease with good response to immunotherapy, hence the importance of a correct diagnosis. Nonetheless, recovery from severe disease may take months to years.

Relapsing Kikuchi-Fujimoto Disease With Hemophagocytic Lymphohistiocytosis.

Kikuchi-Fujimoto disease is a rare, benign, and self-limited disease of uncertain etiology, affecting mostly young female patients. It usually manifests as posterior cervical lymphadenopathy and fever. Its diagnosis is based on typical histopathological changes after the exclusion of other diseases such as lupus, lymphoma, or infectious lymphadenitis. The authors present a 47-year-old female patient with recurring episodes of high fever, urticarial rash, myalgia, arthralgia, fatigue, sore throat, and generalized lymphadenopathy. Blood tests showed increased inflammatory parameters and positive antinuclear antibodies. In the two times the patient was admitted to the hospital there were no infectious agents isolated. The patient didn't fulfill the criteria for diagnosis of lupus or any other autoimmune disease and there was also no evidence of lymphoma or other neoplastic diseases. A positron emission tomography/computed tomography (PET/CT) was performed at the first and second hospitalizations, showing generalized lymphadenopathy. At the first hospitalization, a mediastinal lymph node biopsy was obtained, excluding lymphoproliferative or granulomatous disease. During the course of the second hospitalization, a cervical lymph node was excised for biopsy, the histopathological changes of which suggested the diagnosis of Kikuchi-Fujimoto disease. The clinical course was complicated by hemophagocytic lymphohistiocytosis, with a significant increase in inflammatory markers and liver dysfunction. The patient was treated with prednisolone 1 mg/kg/day, with complete resolution of clinical and biochemical changes.

Masson's Tumour: A Rare Cause of Cervical Mass.

Masson's tumour, also known as intravascular papillary endothelial hyperplasia, is a rare non-neoplastic lesion of vascular origin, caused by an excessive reactive proliferation of endothelial cells in normal blood vessels or vascular malformations. It can affect any part of the body, presenting most frequently in the vessels of the head, neck and upper extremities. The authors describe the case of a 76-year-old female patient presenting an anterior cervical mass, measuring 2×2 cm, which was mobile, tender and slightly painful with no alteration of the overlying skin. Complementary study with ultrasound and computed tomography was inconclusive. Total excision of the lesion was performed with histology compatible with intravascular papillary endothelial hyperplasia. LEARNING POINTS: Masson's tumour is a rare and indolent non-neoplastic lesion of vascular origin, that can be easily confused with other pathological entities and misdiagnosed.Diagnosis can be a challenge; histological characterization is essential for differentiation from other lesions, such as angiosarcoma and Kaposi's sarcoma.Masson's tumour should be considered in patients presenting a single cervical mass.

Are hospitals our friends? An exploratory study on the role of Facebook in hospital organizations' dialogic communication.

Rooted in the dialogic public relations model, the aim of this paper was to analyze the way in which hospital organizations use Facebook to communicate and build relationships with their patients and followers. Using a content analysis of Facebook profiles, there is a reflection on how dialogic principles are applied in the management of Facebook by hospitals in Portugal. Special attention will be paid to communication regarding the Zika virus, which was of public interest at the time the empirical analysis was carried out. The study demonstrates that Portuguese hospitals are present on Facebook but do not use the social network dialogically or to communicate about topical themes of public interest.

Clinicopathologic Characteristics of Patients with Gastric Superficial Neoplasia and Risk Factors for Multiple Lesions after Endoscopic Submucosal Dissection in a Western Country.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a treatment for early gastric neoplasms that preserves the stomach. However, the risk of multiple lesions persists. OBJECTIVES: To assess clinicopathologic characteristics of patients with early gastric neoplasms in a Western country and evaluate risk factors for multiple gastric lesions, synchronous, or metachronous. METHODS: A retrospective cohort of 230 consecutive patients who underwent ESD for primary neoplasms from 2012 to 2017 (median follow-up: 33 months) was assessed to determine the clinicopathologic characteristics and risk factors for multiple lesions. RESULTS: The mean age was 68 years, and 53.9% were male. Current/former smoking status was present in 40.4%, and 29.5% had family history of gastric cancer. A third of the patients had only focal gastric atrophy/metaplasia (operative link on gastritis assessment/operative link on gastric intestinal metaplasia assessment [OLGA/OLGIM] I/II; endoscopic grading of gastric intestinal metaplasia [EGGIM] 1-4). Synchronous and me-tachronous lesions occurred in 14.3 and 8.6% of patients, respectively. There was a trend for higher risk of multiple lesions in smokers and patients with extensive metaplasia (EGGIM >4), but only older age was an independent risk factor (OR 3.30; 95% CI 1.05-10.34). Age >60 years (OR 10.10, 95% CI 1.40-88.04), current/former smoking status (OR 3.64, 95% CI 1.07-12.40), and OLGIM III/IV (OR 3.07, 95% CI 1.01-9.36) were independent risk factors for synchronous lesions. No risk factors for metachronous lesions were found. CONCLUSIONS: Surveillance limited to patients with advanced stages of gastritis may miss some primary superficial neoplasms. Although older age increases the risk of multiple lesions, no risk factors were found for metachronous lesions. Therefore, endoscopic surveillance after ESD should be done equally in all patients.

INTRODUÇÃO: A dissecção endoscópica da submucosa (DES) é uma opção terapêutica para neoplasias gástricas em estadios iniciais e que permite preservar o estômago. No entanto, o risco de desenvolver lesões múltiplas mantém-se. OBJETIVOS: Avaliar as características clinicopatológicas dos pacientes com neoplasias gástricas superficiais primárias num país ocidental e avaliar os fatores de risco (FR) para lesões gástricas múltiplas, síncronas ou metácronas. MÉTODOS: Foram estudados, retrospetivamente, 230 doentes submetidos a DES por lesões gástricas primárias entre 2012 e 2017 (tempo de seguimento mediano: 33 meses). As características clínicopatológicas eos FR para lesões múltiplas foram analisados. RESULTADOS: A idade média foi de 68 anos, 53,9% eram homens, 40,4% eram fumadores/ex-fumadores e 29,5% tinham história familiar de cancro gástrico. Um terço dos pacientes apresentava apenas atrofia/metaplasia focal (OLGA/OLGIM l/ll; EGGIM 1­4). Foram detetadas lesões síncronas em 14,3% e metácronas em 8,6% dos doentes. Para lesões gástricas múltiplas, tabagismo e metaplasia extensa (EGGIM<4) mostraram uma associação, mas apenas a idade avançada foi FR independente (Odds Ratio [OR] 3, 30; Intervalo de Confiança a 95% [IC 95%] 1, 05­10, 34). Idade superior a 60 anos (OR 10,10; IC95% 1,40­88,04), tabagismo (OR 3,64; IC95% 1,07­12,40) e OLGIM lll/IV (OR 3,07; IC95% 1,01­9,36) foram FR independentes para lesões síncronas. Não foram encontrados FR para lesões metácronas. CONCLUSÕES: Limitar a vigilância aos pacientes com gastrite em estadios avançados não permite identificar todas as lesões neoplásicas precoces. A idade avançada aumenta o risco de lesões múltiplas, contudo não foi encontrado nenhum FR para lesões metácronas. Assim, a vigilância endoscópica após DES deve ser idêntica em todos os pacientes.

Endoscopic grading of gastric intestinal metaplasia on risk assessment for early gastric neoplasia: can we replace histology assessment also in the West?

OBJECTIVES: To assess the value of endoscopic grading of gastric intestinal metaplasia (EGGIM), operative link on gastritis assessment (OLGA) and operative link on gastric intestinal metaplasia (OLGIM) on risk stratification for early gastric neoplasia (EGN) and to investigate other factors possibly associated with its development. DESIGN: Single centre, case-control study including 187 patients with EGN treated endoscopically and 187 age-matched and sex-matched control subjects. Individuals were classified according to EGGIM, OLGA and OLGIM systems. EGN risk according to gastritis stages and other clinical parameters was further evaluated. RESULTS: More patients with EGN had EGGIM of ≥5 than control subjects (68.6% vs 13.3%, p<0.001). OLGA and OLGIM stages III/IV were more prevalent in patients with EGN than in control subjects (68% vs 11%, p<0.001, and 61% vs 3%, p<0.001, respectively). The three systems were the only parameters significantly related to the risk of EGN in multivariate analysis: for EGGIM 1-4 (adjusted OR (AOR) 12.9, 95% CI 1.4 to 118.6) and EGGIM 5-10 (AOR 21.2, 95% CI 5.0 to 90.2); for OLGA I/II (AOR 5.0, 95% CI 0.56 to 44.5) and OLGA III/IV (AOR 11.1, 95% CI 3.7 to 33.1); for OLGIM I/II (AOR 11.5, 95% CI 4.1 to 32.3) and OLGIM III/IV (AOR 16.0, 95% CI 7.6 to 33.4). CONCLUSION: This study confirms the role of histological assessment as an independent risk factor for gastric cancer (GC), but it is the first study to show that an endoscopic classification of gastric intestinal metaplasia is highly associated with that outcome. After further prospective validation, this classification may be appropriate for GC risk stratification and may simplify every day practice by reducing the need for biopsies.

A novel V(IV)O-pyrimidinone complex: synthesis, solution speciation and human serum protein binding.

The pyrimidinones mhcpe, 2-methyl-3H-5-hydroxy-6-carboxy-4-pyrimidinone ethyl ester (mhcpe, 1), 2,3-dimethyl-5-benzyloxy-6-carboxy-4-pyrimidinone ethyl ester (dbcpe, 2) and N-methyl-2,3-dimethyl-5-hydroxy-6-carboxyamido-4-pyrimidinone (N-MeHOPY, 3), are synthesized and their structures determined by single crystal X-ray diffraction. The acid-base properties of 1 are studied by potentiometric and spectrophotometric methods, the pK(a) values being 1.14 and 6.35. DFT calculations were carried out to determine the most stable structure for each of the H2L(+), HL and L(-) forms (HL = mhcpe) and assign the groups involved in the protonation-deprotonation processes. The mhcpe(-) ligand forms stable complexes with V(IV)O(2+) in the pH range 2 to 10, and potentiometry, EPR and UV-Vis techniques are used to identify and characterize the V(IV)O-mhcpe species formed. The results are consistent with the formation of V(IV)O, (V(IV)O)L, (V(IV)O)L2, (V(IV)O)2L2H(-2), (V(IV)O)L2H(-1), (V(IV)O)2L2H(-3), (V(IV)O)LH(-2) species and V(IV)O-hydrolysis products. Calculations indicate that the global binding ability of mhcpe towards V(IV)O(2+) is similar to that of maltol (Hmaltol = 3-hydroxy-2-methyl-4H-pyran-4-one) and lower than that of 1,2-dimethyl-3-hydroxy-4-pyridinone (Hdhp). The interaction of V(IV)O-complexes with human plasma proteins (transferrin and albumin) is studied by circular dichroism (CD), EPR and (51)V NMR spectroscopy. V(IV)O-mhcpe-protein ternary complexes are formed in both cases. The binding of V(IV)O(2+) to transferrin (hTF) in the presence of mhcpe involves mainly (V(IV)O)1(hTF)(mhcpe)1, (V(IV)O)2(hTF)(mhcpe)1 and (V(IV)O)2(hTF)(mhcpe)2 species, bound at the Fe(III) binding sites, and the corresponding conditional formation constants are determined. Under the conditions expected to prevail in human blood serum, CD data indicate that the V(IV)O-mhcpe complexes mainly bind to hTF; the formation of V(IV)O-hTF-mhcpe complexes occurs in the presence of Fe(III) as well, distinct EPR signals being clearly obtained for Fe(III)-hTF and to V(IV)O-hTF-mhcpe species. Thus this study indicates that transferrin plays the major role in the transport of V(IV)O-mhcpe complexes under blood plasma conditions in the form of ternary V(IV)-ligand-protein complexes.

Interaction of vanadium(IV) with human serum apo-transferrin.

The interaction of V(IV)O-salts as well as of a few V(IV)O(carrier)n complexes with human serum transferrin (hTF) is studied focusing on the determination of the nature and stoichiometry of the binding of V(IV)O(2+) to hTF, as well as whether the conformation of hTF upon binding to V(IV)O(2+) or to its complexes is changed. Circular dichroism (CD) spectra measured for solutions containing V(IV)O(2+) and apo-hTF, and V(IV)O-maltol and apo-hTF, clearly indicate that hTF-V(IV)O-maltol ternary species form with a V(IV)O:maltol stoichiometry of 1:1. For V(IV)O salts and several V(IV)O(carrier)n complexes (carrier ligand=maltolato, dhp, picolinato and dipicolinato) (Hdhp=1,2-dimethyl-3-hydroxy-4-pyridinone) the maximum number of V(IV)O(2+) bound per mole of hTF is determined to be ~2 or lower in all cases. The binding of V(IV)O to apo-hTF most certainly involves several amino acid residues of the Fe-binding site, and as concluded by urea gel electrophoresis experiments, the formation of (V(IV)O)2hTF species may occur with the closing of the hTF conformation as is the case in (Fe(III))2hTF, which is an essential feature for the transferrin receptor recognition.

Association of interleukin 1ß polymorphisms and haplotypes with Alzheimer's disease.

Our study aimed to associate IL-1ß and IL-1RN polymorphisms with AD disease in comparison with elderly control group from São Paulo - Brazil. We genotyped 199 Alzheimer's disease (AD) patients, 165 elderly control and 122 young control samples, concerning VNTR (IL-1RN) and -511C>T and -31T>C (IL-1ß) polymorphisms. Our findings revealed that -511C/-31T/2-repetitions VNTR haplotype had a protective effect for AD when compared to EC (p=0.005), whereas -511C/-31C/1-repetition VNTR haplotype was associated as a risk factor for AD (p=0.021). Taken together, we may suggest that there is a relevant role of IL-1 genes cluster in AD pathogenesis in this Brazilian population.

Biocatalytic formation of synthetic melanin: the role of vanadium haloperoxidases, L-DOPA and iodide.

The vanadium haloperoxidase (V-HPO) enzyme, extracted from the brown alga Laminaria saccharina, is able to catalyze the formation of a black precipitate, using as precursor the amino acid L-dopa in the presence of hydrogen peroxide and iodide, in one-pot synthesis. The L-dopa oxidation is a multistep reaction with a crucial role played by the iodide in the enzyme catalyzed peroxidative production of dopachrome, a well known intermediate in the synthesis of melanin. Dopachrome is then converted to a synthetic form of melanin through a polymerization reaction. Factors, such as buffer composition and pH, influence significantly the reaction first steps, but further steps of melanin production are hardly influenced. The biosynthetic melanin produced through the combination V-HPO/I/H(2)O(2), was characterized by several spectroscopic techniques (UV-vis and FT-IR) as well as XRD. Moreover, this biopolymer is light sensitive, decomposing into oligo- and monomeric units. Scanning electron microscopy (SEM) imaging showed different morphologies when compared with commercial available melanin. The biosynthetic production of melanin can have a wide range of applications from photosensitive cells to biomedicine with the advantage of being produced under eco-friendly and mild conditions.

Vanadium compounds as therapeutic agents: some chemical and biochemical studies.

The behaviour of three vanadium(V) systems, namely the pyridinone (V(V)-dmpp), the salicylaldehyde (V(V)-salDPA) and the pyrimidinone (V(V)-MHCPE) complexes, is studied in aqueous solutions, under aerobic and physiological conditions using (51)V NMR, EPR and UV-Visible (UV-Vis) spectroscopies. The speciations for the V(V)-dmpp and V(V)-salDPA have been previously reported. In this work, the system V(V)-MHCPE is studied by pH-potentiometry and (51)V NMR. The results indicate that, at pH ca. 7, the main species present are (V(V)O(2))L(2) and (V(V)O(2))LH(-1) (L=MHCPE(-)) and hydrolysis products, similar to those observed in aqueous solutions of V(V)-dmpp. The latter species is protonated as the pH decreases, originating (V(V)O(2))L and (V(V)O(2))LH. All the V(V)-species studied are stable in aqueous media with different compositions and at physiological pH, including the cell culture medium. The compounds were screened for their potential cytotoxic activity in two different cell lines. The toxic effects were found to be incubation time and concentration dependent and specific for each compound and type of cells. The HeLa tumor cells seem to be more sensitive to drug effects than the 3T3-L1 fibroblasts. According to the IC(50) values and the results on reversibility to drug effects, the V(V)-species resulting from the V(V)-MHCPE system show higher toxicity in the tumor cells than in non-tumor cells, which may indicate potential antitumor activity.