A 2-week treatment with 5-azacytidine improved the hypercontractility state in prostate from obese mice: Role of the nitric oxide-cyclic guanosine monophosphate signalling pathway.

Benign prostatic hyperplasia (BPH) is characterised by increases in prostate volume and contraction. Downregulation of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signalling pathway contributes to prostate dysfunctions. Previous studies in cancer cells or vessels have shown that the epigenetic mechanisms control the gene and protein expression of the enzymes involved in the production of NO and cGMP. This study is aimed to evaluate the effect of a 2-week treatment of 5-azacytidine (5-AZA), a DNA-methyltransferase inhibitor, in the prostate function of mice fed with a high-fat diet. Functional, histological, biochemical and molecular assays were carried out. Obese mice presented greater prostate weight, α-actin expression and contractile response induced by the α-1adrenoceptors agonist. The relaxation induced by the NO-donor and the protein expression of endothelial nitric oxide synthase (eNOS) and soluble guanylate cyclase (sGC) were significantly decreased in the prostate of obese mice. The treatment with 5-AZA reverted the higher expression of α-actin, reduced the hypercontractility state of the prostate and increased the expression of eNOS and sGC and intraprostatic levels of cGMP. When prostates from obese mice treated with 5-AZA were incubated in vitro with inhibitors of the NOS or sGC, the inhibitory effect of 5-AZA was reverted, therefore, showing the involvement of NO and cGMP. In conclusion, our study paves the way to develop or repurpose therapies that recover the expression of eNOS and sGC and, hence, to improve prostate function in BPH.

Association of single nucleotide variants in VEGFA and KDR with the risk and angiogenic features of diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype and dependent on angiogenesis (AG), whose main effectors are VEGFA and VEGFR2. Functional single nucleotide variants (SNVs) are described in VEGFA and KDR genes. However, it still unknown whether VEGFA - 2578C/A, -2489C/T, -1154G/A, -634G/C, -460C/T and KDR-604T/C, -271G/A, +1192G/A and +1719A/T SNVs act on DLBCL risk and angiogenic features. Genomic DNA from 168 DLBCL patients and 205 controls was used for SNV genotyping. Angiogenesis was immunohistochemically assessed in tumor biopsies, with reactions for VEGFA, VEGFR2, and CD34. VEGFA -1154GG genotype were associated with 1.6-fold higher DLBCL risk. KDR + 1192GG plus KDR + 1719 TT and KDR + 1192GG plus VEGFA - 2578CC combined genotypes are associated with 2.19- and 2.04-fold higher risks of DLBCL, respectively. VEGFA - 634GG or GC genotypes are associated with increased microvessel density and VEGFA levels. No relationship was observed between SNVs and cell-of-origin classification of DLBCL, but higher VEGFA and VEGFR2 were seen in non-germinal center tumors.

Identifying cellular markers of focal cortical dysplasia type II with cell-type deconvolution and single-cell signatures.

Focal cortical dysplasia (FCD) is a brain malformation that causes medically refractory epilepsy. FCD is classified into three categories based on structural and cellular abnormalities, with FCD type II being the most common and characterized by disrupted organization of the cortex and abnormal neuronal development. In this study, we employed cell-type deconvolution and single-cell signatures to analyze bulk RNA-seq from multiple transcriptomic studies, aiming to characterize the cellular composition of brain lesions in patients with FCD IIa and IIb subtypes. Our deconvolution analyses revealed specific cellular changes in FCD IIb, including neuronal loss and an increase in reactive astrocytes (astrogliosis) when compared to FCD IIa. Astrogliosis in FCD IIb was further supported by a gene signature analysis and histologically confirmed by glial fibrillary acidic protein (GFAP) immunostaining. Overall, our findings demonstrate that FCD II subtypes exhibit differential neuronal and glial compositions, with astrogliosis emerging as a hallmark of FCD IIb. These observations, validated in independent patient cohorts and confirmed using immunohistochemistry, offer novel insights into the involvement of glial cells in FCD type II pathophysiology and may contribute to the development of targeted therapies for this condition.

Optimized multiplex immunofluorescence for the characterization of tumor immune microenvironment in neoplastic paraffin-preserved tissues.

The study of neoplastic cells enabled the discovery of important tumor-related biomarkers which resulted in new forms of early diagnosis, therapeutic options, and prognostic markers. Thus, immunofluorescence (IF), a high throughput imaging technology, represents a valuable method that enables the virtual characterization and localization of diverse cell types and targets, preserving tissue architecture and spatial surroundings. IF staining and analysis of formalin-fixed paraffin-embedded (FFPE) tissues are considered a challenge due to several difficulties, such as tissue autofluorescence, non-specific antibody binding, and image acquisition and quality. This study aimed to develop a multiplex-fluorescence staining technique with high-contrast and high-quality multiple-color images to enrich the investigation of important biomarkers. We present a robust optimized multiple-immunofluorescence procedure that reduced sample autofluorescence, enabled the use of simultaneous antibodies on the same sample, and showed super-resolution imaging through precise antigen localization. We illustrated the utility of this powerful method in FFPE neoplastic appendix, lymph node and bone marrow biopsies, and a 3D-coculture system, in which cells are enabled to grow and interact with their surroundings in all 3D dimensions. Our optimized multiple-immunofluorescence method represents a powerful tool for better understanding the complexity of tumor cells, characterizing cell populations and spatial localization, revealing predictive and prognostic biomarkers, and identifying immunologic phenotypes in a single and limited sample. This valuable IF protocol successfully enables tumor microenvironment profiling that could contribute to the study of cellular crosstalk and the niche, and to the identification of predictive biomarkers for neoplasms.

Autoimmune hepatitis and primary biliary cholangitis overlap syndrome after COVID-19.

COVID-19 is commonly associated with high serum levels of pro-inflammatory cytokines, and the post-infection status can disturb self-tolerance and trigger autoimmune responses. We are reporting a 45-year-old male who was admitted with fatigue, jaundice, elevated liver enzymes (with cholestatic pattern), and acute kidney injury two weeks after recovering from a mild SARS-CoV-2 infection. Serologies for viral hepatitis and anti-mitochondrial antibody were negative, while anti-nuclear and anti-smooth muscle antibodies were positive. There were no signs of chronic liver disease, and a magnetic resonance cholangiography showed no dilatation of biliary ducts. Histologic evaluation of the liver evidenced numerous foci of lobular necrosis without ductopenia or portal biliary reaction. Considering the autoantibody profile and histologic changes, the medical team started oral prednisone, but there was a suboptimal biochemical response in the outpatient follow-up. Two months later, a second liver biopsy was performed and revealed non-suppurative destructive chronic cholangitis, extensive areas of confluent necrosis with hepatocytes regenerating into pseudorosettes, and numerous plasma cells. According to the Paris Criteria, the patient was then diagnosed with an autoimmune hepatitis-primary biliary cholangitis overlap syndrome (AIH-PBC-OS). After adding azathioprine and ursodeoxycholic acid to the treatment, there was a satisfactory response. This is the second worldwide report of an AIH-PBC-OS triggered by COVID-19, but the first case with a negative anti-mitochondrial antibody. In this setting, histologic evaluation of the liver by an experienced pathologist is a hallmark of achieving the diagnosis and correctly treat the patient.

Transcriptome analyses of the cortex and white matter of focal cortical dysplasia type II: Insights into pathophysiology and tissue characterization.

Introduction: Focal cortical dysplasia (FCD) is a common cause of pharmacoresistant epilepsy. According to the 2022 International League Against Epilepsy classification, FCD type II is characterized by dysmorphic neurons (IIa and IIb) and may be associated with balloon cells (IIb). We present a multicentric study to evaluate the transcriptomes of the gray and white matters of surgical FCD type II specimens. We aimed to contribute to pathophysiology and tissue characterization. Methods: We investigated FCD II (a and b) and control samples by performing RNA-sequencing followed by immunohistochemical validation employing digital analyses. Results: We found 342 and 399 transcripts differentially expressed in the gray matter of IIa and IIb lesions compared to controls, respectively. Cholesterol biosynthesis was among the main enriched cellular pathways in both IIa and IIb gray matter. Particularly, the genes HMGCS1, HMGCR, and SQLE were upregulated in both type II groups. We also found 12 differentially expressed genes when comparing transcriptomes of IIa and IIb lesions. Only 1 transcript (MTRNR2L12) was significantly upregulated in FCD IIa. The white matter in IIa and IIb lesions showed 2 and 24 transcripts differentially expressed, respectively, compared to controls. No enriched cellular pathways were detected. GPNMB, not previously described in FCD samples, was upregulated in IIb compared to IIa and control groups. Upregulations of cholesterol biosynthesis enzymes and GPNMB genes in FCD groups were immunohistochemically validated. Such enzymes were mainly detected in both dysmorphic and normal neurons, whereas GPNMB was observed only in balloon cells. Discussion: Overall, our study contributed to identifying cortical enrichment of cholesterol biosynthesis in FCD type II, which may correspond to a neuroprotective response to seizures. Moreover, specific analyses in either the gray or the white matter revealed upregulations of MTRNR2L12 and GPNMB, which might be potential neuropathological biomarkers of a cortex chronically exposed to seizures and of balloon cells, respectively.

Autoimmune hepatitis and primary biliary cholangitis overlap syndrome after COVID-19

ABSTRACT COVID-19 is commonly associated with high serum levels of pro-inflammatory cytokines, and the post-infection status can disturb self-tolerance and trigger autoimmune responses. We are reporting a 45-year-old male who was admitted with fatigue, jaundice, elevated liver enzymes (with cholestatic pattern), and acute kidney injury two weeks after recovering from a mild SARS-CoV-2 infection. Serologies for viral hepatitis and anti-mitochondrial antibody were negative, while anti-nuclear and anti-smooth muscle antibodies were positive. There were no signs of chronic liver disease, and a magnetic resonance cholangiography showed no dilatation of biliary ducts. Histologic evaluation of the liver evidenced numerous foci of lobular necrosis without ductopenia or portal biliary reaction. Considering the autoantibody profile and histologic changes, the medical team started oral prednisone, but there was a suboptimal biochemical response in the outpatient follow-up. Two months later, a second liver biopsy was performed and revealed non-suppurative destructive chronic cholangitis, extensive areas of confluent necrosis with hepatocytes regenerating into pseudorosettes, and numerous plasma cells. According to the Paris Criteria, the patient was then diagnosed with an autoimmune hepatitis-primary biliary cholangitis overlap syndrome (AIH-PBC-OS). After adding azathioprine and ursodeoxycholic acid to the treatment, there was a satisfactory response. This is the second worldwide report of an AIH-PBC-OS triggered by COVID-19, but the first case with a negative anti-mitochondrial antibody. In this setting, histologic evaluation of the liver by an experienced pathologist is a hallmark of achieving the diagnosis and correctly treat the patient.

Oral follicular lymphoma: a clinicopathologic and molecular study.

Follicular lymphoma is a hematolymphoid neoplasm that originates from germinal center B cells. It is made up of a combination of small cleaved centrocytes and a varying quantity of larger non-cleaved centroblasts to describe the clinical, microscopic, immunohistochemical, and molecular features of oral follicular lymphomas. Follicular lymphomas affecting the oral cavity were retrieved from pathology files. Immunohistochemistry was performed to confirm the diagnosis, and fluorescence in situ hybridization (FISH) was employed to detect rearrangements in BCL2, BCL6, and MYC genes. Clinical and follow-up data were obtained from the patient's medical and pathology files. Twenty cases were obtained. There was an equal sex distribution (10 males: 10 females) and a mean age of 60.9 years (range: 10-83 years-old). Lesions presented as asymptomatic swellings, usually in the palate (10 cases) and the buccal mucosa (7 cases). Five patients presented with concomitant nodal involvement. Microscopic evaluation depicted the follicular growth pattern with diffuse areas in six cases. Grades 1 and 2 follicular lymphomas represented 12 cases, while grade 3A neoplasms accounted for other 8 cases. Two cases showed rearrangements in MYC, BCL2, and BCL6 genes, while single BCL2 translocation was found in eight cases. Two cases had no translocation. Three patients deceased and the 2-year overall survival achieved 88%. Follicular lymphoma affecting the oral cavity is uncommon, usually affects the palate as a non-ulcerated swelling and the presence of a systemic disease most always be ruled out.

Novel inhibitor of hematopoietic cell kinase as a potential therapeutic agent for acute myeloid leukemia.

Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are characterized by risk of relapses, poor survival, unwanted side effects and high toxicity with the current therapies. In light of these facts, there are efforts to develop new drugs specific for deregulated molecules that participate in leukemia pathogenesis. Hematopoietic cell kinase (HCK), an Src kinase family member, is overexpressed on hematopoietic stem cells of MDS and de novo AML patients and involved in the oncogenic process. Thus, we investigated in vitro, ex vivo and in vivo effects of a novel chemical compound targeting HCK inhibition (iHCK-37), in combination with the most used drugs for the treatment of MDS and de novo AML, 5-Azacytidine and Cytarabine. Herein, the combination treatment with iHCK-37 and 5-Azacytidine or Cytarabine demonstrated additive effects against leukemia cells, compared to either drug alone. iHCK-37 plus 5-Azacytidine or Cytarabine treatment was able to reduce the activation of oncogenic pathways, MAPK/ERK and PI3K/AKT, leading to reduction of ERK and AKT phosphorylation, and increased BAX and decreased BCL-XL protein expression. Moreover, treatment with iHCK-37 reduced MDS and AML CD34-positive cell numbers inside a 3D-structure but did not affect normal CD34-positive cell numbers. In vivo analysis showed that leukemic mice treated with iHCK-37 had reduced ERK and AKT proteins phosphorylation levels and leukocyte numbers. In conclusion, the iHCK-37 inhibitor has anti-neoplastic activity in leukemia cells without altering apoptosis and survival rate of normal cells, suggesting on-target malignant cell killing activity as a single agent or in combination with 5-Azacytidine or Cytarabine.

Fumarate hydratase-deficient renal cell carcinoma: A tumor with diverse morphology including cannibalism, lymphocytic emperipolesis, and defective autophagy.

We report the clinicopathological findings of the first series of 3 patients from Brazil with fumarate hydratase-deficient renal cell carcinoma. The clinicopathological findings disclosed a very aggressive tumor. All 3 patients had solitary tumor at the left side, metastasis and advanced stage at the time of diagnosis; were females with a median age of 40 years; had a history of uterine leiomyomas; and, at follow-up two patients are deceased and one patient alive. The microscopic findings of these 3 patients are in accordance with the literature disclosing a variety of morphologic features being papillary arrangement, eosinophilic cytoplasm, and prominent nucleoli surrounded by clear halo the constant and most frequent findings. Previously not reported in this tumor, we describe presence of cannibalism, lymphocytic emperipolesis, and cytoplasmic vacuoles with eosinophilic inclusions associated with overexpression of p62 in immunohistochemistry which is considered to be evidence of defective autophagy. Lymphocytic emperipolesis was a more frequent finding than cannibalism and immunohistochemistry for p62 was overexpressed only in the 2 patients disclosing cytoplasmic vacuoles with eosinophilic inclusions. The presence, frequency and significance of these novel findings should be checked in large series of this rare and aggressive tumor aiming to associate with clinical behavior and eventually influence the strategy of treatment.

Expression of Amphiregulin in Enchondromas and Central Chondrosarcomas.

OBJECTIVES: The aim of this study was to evaluate the role of amphiregulin protein, an epidermal growth factor receptor ligand, in cartilaginous tumors. METHODS: Amphiregulin expression was examined in 31 enchondromas and 67 chondrosarcomas using immunohistochemistry analysis. RESULTS: Overall, 15 enchondromas (48.40%) and 24 chondrosarcomas (35.82%) were positive for amphiregulin. According to the receiver operating characteristic curve test, no difference in amphiregulin expression was observed between enchondromas and low-grade chondrosarcomas (p=0.0880). Additionally, 39 lesions (16 in short bones, 13 in long bones, and 10 in flat bones) were positive for amphiregulin, exhibiting a higher percentage of positive cells (p=0.0030) and intensity of immunohistochemical expression (p=0.0055) in short bone lesions than in others. Among 25 enchondromas localized in short bones, 15 expressed amphiregulin; however, all 6 cases localized in long bones were negative for this marker (p=0.0177). CONCLUSIONS: Amphiregulin did not help in distinguishing enchondromas from low-grade chondrosarcomas. The present study is the first to document the expression of this immunohistochemical marker in enchondromas. Furthermore, amphiregulin expression in enchondromas was localized in short bones, indicating a phenotypic distinction from that in long bones. This distinction may contribute to an improved understanding of the pathogenesis of these lesions.

Mycobacterium infection as a mimicker of brain metastasis.

Mycobacterium infection is a differential diagnosis to be considered in brain multifocal lesions with peripheral enhancement.

Single nucleotide variants in immune-response genes and the tumor microenvironment composition predict progression of mantle cell lymphoma.

BACKGROUND: There is evidence to consider that the tumor microenvironment (TME) composition associates with antitumor immune response, and may predict the outcome of various non-Hodgkin lymphoma subtypes. However, in the case of mantle cell lymphoma (MCL), a rare and aggressive disease, there is lacking a detailed study of the TME components, as well as an integrative approach among them in patients' samples. Also, from the genetic point of view, it is known that single nucleotide variants (SNVs) in immune-response genes are among important regulators of immunity. At present, it is uncertain whether SNVs in candidate immune-response genes and the TME composition are able to alter the prognosis in MCL. METHODS: We assessed a detailed TME composition in 88 MCL biopsies using immunohistochemistry, which was automatically analyzed by pixel counting (Aperio system). We also genotyped SNVs located in candidate immune-response genes (IL12A, IL2, IL10, TGFB1, TGFBR1, TGFBR2, IL17A, IL17F) in 95 MCL patients. We tested whether the SNVs could modulate the respective protein expression and TME composition in the tumor compartment. Finally, we proposed survival models in rituximab-treated patients, considering immunohistochemical and SNV models. RESULTS: High FOXP3/CD3 ratios (p = 0.001), high IL17A levels (p = 0.003) and low IL2 levels (p = 0.03) were individual immunohistochemical predictors of poorer survival. A principal component, comprising high quantities of macrophages and high Ki-67 index, also worsened outcome (p = 0.02). In the SNV model, the CC haplotype of IL10 (p < 0.01), the GG genotype of IL2 rs2069762 (p = 0.02) and the AA+AG genotypes of TGFBR2 rs3087465 (p < 0.01) were independent predictors of outcome. Finally, the GG genotype of TGFB1 rs6957 associated with lower tumor TGFß levels (p = 0.03) and less CD163+ macrophages (p = 0.01), but did not modulate patients' survival. CONCLUSIONS: Our results indicate that the TME composition has relevant biological roles in MCL. In this setting, immunohistochemical detection of T-reg cells, IL17A and IL2, coupled with SNV genotyping in IL10, TGFBR2 and IL2, may represent novel prognostic factors in this disease, following future validations.

New germline GATA1 variant in females with anemia and thrombocytopenia.

Familial forms of bone marrow defects are rare disorders and description of new cases are valuable opportunities to clarify the molecular machinery that triggers hematopoiesis and blood formation, as well as risk to malignant transformation. We investigated the genetic scenario and possible patterns of transmission in a rare case of familial myeloid disorder with a history of exposure to pesticides. Blood counts of two proband sisters, age 41 and 42, revealed mild anemia, neutrophilia and thrombocytopenia with bone marrow finding mimicking primary myelofibrosis in the cellular phase. We analyzed the coding regions of 78 myeloid neoplasms-related genes and 16 encoding xenobiotic metabolizing genes using Next-Generation Sequencing. The GATA1 variant c.788C > T, p.T263M, located in the C-terminal zinc finger domain of GATA1, was detected in the DNA of the two sisters. The screening of the other kindreds also revealed the p.T263M variant in the mother and two daughters with the same bone marrow disorder. This is the first report of an alteration in the GATA1 CF domain causing anemia, thrombocytopenia and megakaryocyte proliferation with mild myelofibrosis, correlating a new GATA1 germline variant with myeloid disorder.

Quality of life and the work capacity of professional nursing staff in the hospital environment

This study aimed to evaluate the association between life quality and the work capacity of nursing professionals in a public hospital of the public health system. A cross-sectional, quantitative study with the participation of 115 nursing professionals. The study method used the WHOQOL-brief questionnaire, the Work Capacity Index questionnaire, and a sociodemographic and occupational questionnaire. The data were analyzed through descriptive and inferential statistics, where values of p≤ 0.05 were considered significant. In terms of life quality, the domains that presented higher averages were for psychological 70.0±14.5 and social relations 70.8±19.8, with the physical domain reaching 64.4±11.9 and the environment at 57.7±13.6. The average score from the Work Capacity Index was 40.3±6.1; median: 42; IQR: 37.0-45.0), with a predominance of good and excellent for work capacity. Work capacity was increased for being male (ß=3.99; p=0.016) and negatively associated to age (ß=-0.31; p<0.001). In conclusion, it is verified that there is a positive correlation between the capacity for work and the evaluation of the quality of life, but it is emphasized that the sociodemographic and occupational characteristics lead the nursing professional to present a work capacity reduction, which generates alterations in the perception of life quality.

Expression of amphiregulin in enchondromas and central chondrosarcomas

OBJECTIVES: The aim of this study was to evaluate the role of amphiregulin protein, an epidermal growth factor receptor ligand, in cartilaginous tumors. METHODS: Amphiregulin expression was examined in 31 enchondromas and 67 chondrosarcomas using immunohistochemistry analysis. RESULTS: Overall, 15 enchondromas (48.40%) and 24 chondrosarcomas (35.82%) were positive for amphiregulin. According to the receiver operating characteristic curve test, no difference in amphiregulin expression was observed between enchondromas and low-grade chondrosarcomas (p=0.0880). Additionally, 39 lesions (16 in short bones, 13 in long bones, and 10 in flat bones) were positive for amphiregulin, exhibiting a higher percentage of positive cells (p=0.0030) and intensity of immunohistochemical expression (p=0.0055) in short bone lesions than in others. Among 25 enchondromas localized in short bones, 15 expressed amphiregulin; however, all 6 cases localized in long bones were negative for this marker (p=0.0177). CONCLUSIONS: Amphiregulin did not help in distinguishing enchondromas from low-grade chondrosarcomas. The present study is the first to document the expression of this immunohistochemical marker in enchondromas. Furthermore, amphiregulin expression in enchondromas was localized in short bones, indicating a phenotypic distinction from that in long bones. This distinction may contribute to an improved understanding of the pathogenesis of these lesions.

Severe cardiac insufficiency secondary to cardiotoxicity with clinical and morpho-functional improvement after optimised clinical treatment: case report / Insuficiência cardíaca grave secundária a cardiotoxicidade com melhora clínica e morfo-funcional após tratamento clínico otimizado: relato de caso

Many therapies used for cancer (pathology whose cases are progressively increasing in the world) such as chemotherapy and radiotherapy have numerous adverse effects, with cardiotoxicity being one of the most important. This can be defined from the detection, by an imaging method, of a reduction of at least 10% in the left ventricular ejection fraction (LVEF), bringing it to a value below 53%. Anthracyclines (such as Doxorubicin), Trastuzumab, and Taxanes (Docetaxel) are among the most associated chemotherapeutics. To emphasize the importance of optimized treatment for heart failure and to review the main updates on the theme of cardiotoxicity. Case report and bibliographic review on the latest updates to the management of cardiotoxicity and associated heart failure. When correctly identifying the main risk factors associated with chemotherapy and the individual to develop myocardial injury, it is possible to perform the monitoring by means of two main predictors: the myocardial tension strength and the biomarkers. In this sense, changes associated with these predictors may allow early intervention through appropriate treatment and, with the advancement of research, even prevention, mainly using the association of Carvedilol with Enalapril. Continuous monitoring and early initiation of drug therapy for heart failure are clearly associated with a lower degree of myocardial injury and a lower rate of complications. In addition, there is still an increasingly promising possibility in relation to preventive drug therapy, however, there is still a lack of studies on this topic.

Muitas terapias utilizadas para o câncer (patologia cujos casos estão aumentando progressivamente no mundo) como a quimioterapia e a radioterapia possuem inúmeros efeitos adversos, sendo a cardiotoxicidade um dos mais importantes. Esta pode ser definida a partir da detecção, por um método de imagem, de uma redução de, pelo menos, 10% na fração de ejeção do ventrículo esquerdo (FEVE), levando a mesma para um valor inferior a 53%. As Antraciclinas (como a Doxorrubicina), o Trastuzumab, e os Taxanos (Docetaxel) estão entre os quimioterápicos mais associados. Enfatizar a importância do tratamento otimizado para insuficiência cardíaca e revisar sobre as principais atualizações do tema cardiotoxicidade. Relato de caso e revisão bibliográfica sobre últimas atualizações de condutas referentes ao manejo da cardiotoxicidade e insuficiência cardíaca associada. Ao se identificar corretamente os principais fatores de risco associados à quimioterapia e ao indivíduo para desenvolver a injúria miocárdica, é possível realizar o monitoramento por meio de dois preditores principais: a força de tensão miocárdica e os biomarcadores. Nesse sentido, alterações associadas a esses preditores podem permitir a intervenção precoce por meio do tratamento adequado e, com o avanço das pesquisas, até mesmo a realização da prevenção, principalmente utilizando-se a associação de Carvedilol com Enalapril. Monitorização contínua e início precoce da terapia medicamentosa para insuficiência cardíaca estão claramente associadas com um menor grau de injúria miocárdica e um menor índice de complicações. Além disso, ainda há a possibilidade cada vez mais promissora em relação à terapia medicamentosa preventiva, porém, ainda há carência de estudos em relação a este tema.

Multiresistant microorganism infection in newborns at an intermediate neonatal care unit and intensive care unit of reference: cross-sectional study / Infecção por microrganismo multirresistente em recém-nascidos na unidade de cuidados intermediários neonatais e unidade de cuidados intensivos de referência: estudo transversal

The objective was to describe the infection profile of multidrug-resistant organisms of newborns (NB), admitted to the neonatal intermediate care unit and the intensive care unit. It was a descriptive cross-sectional study of epidemiological nature, composed of 931 medical records and/or Hospital Infection Control Committee notification records, during the period of June to September 2012. Eight hundred and seventy newborns (NB) were admitted to the neonatal intensive care units and to intermediate care, with a final sample of 45 NB presenting bloodstream infections (BSI) caused by multiresistant microorganisms. From the analyses, the following results were highlighted: gestational age < 37 weeks in 42 (93.3%); low weight at birth between < 750g to 1.499g. The profile for resistance to enterobacteriaceae was 100% for cefepime and ceftazidime concerning non-fermenting gram-negative bacteria, it was found that (100%) of P.aeruginosa was resistant to aztreonam, (100%) of S. maltophilia resistant to ceftazidime and to gentamycin, however, (1.1%) of S. aureus isolates were resistant to oxacillin and (12.5%) of S. haemolyticus demonstrated a confirmed resistance to vancomycin. These results are worrying and express the importance of correct monitoring, and the need for producing a propaedeutic protocol in consensus with the multiprofessional team through the Hospital Infection Control Committee and managers, which is then implemented and regularly assessed by the service.

Objetivou-se descrever a infecção por microorganismo multirresistente em recém-nascidos na unidade de cuidados intermediários neonatais e unidade de cuidados intensivos de referência. Tratou-se de estudo transversal de natureza epidemiológica, composto por 931 fichas e/ou prontuários de notificação da Comissão de Controle de Infecção Hospitalar (CCIH), no período junho a setembro de 2012. Foram 870 recém-nascidos (RN), admitidos nas unidades de terapia intensiva neonatal e de cuidados intermediários, como amostra final 45 RN apresentaram infecção de corrente sanguínea por microorganismo multirresistente. Dessas análises destacam-se os resultados: idade gestacional < 37 semanas em 42 (93,3%); baixo peso ao nascer entre < 750g a 1.499g. O perfil de resistência à enterobactérias foi de 100% para o cefepime e ceftazidime, e para as bactérias gram-negativas não fermentadoras, verificou-se que (100%) da P.aeruginosa era resistente ao aztreonam, (100%) de S.maltophilia resistente à ceftazidima e à gentamicina; Entretanto, (1,1%) dos isolados de S. aureus eram resistentes à oxacilina e (12,5%) de S. haemolyticus conferiu resistência à vancomicina. Esses resultados são preocupantes e demonstram a relevância do monitoramento, propondo a elaboração de protocolo propedêutico em consenso com a equipe multiprofissional, com a CCIH e gestores a ser implementado e avaliado, regularmente pelo serviço.

Nutritional profile and biochemical alterations in non-institutionalized senior citizens with Alzheimer disease: a case-control study / Perfil nutricional e alterações bioquímicas em idosos com doença de Alzheimer não institucionalizados: um estudo caso-controle

Assess the nutritional and biochemical state of patients with Alzheimer Disease (AD) compared to a control group. This is an observational, case-control and descriptive type study, based on the recruiting of 22 elderly individuals with a clinical diagnosis of AD considered as the case group, and 22 other elderly individuals considered as the control group. Evaluations were made using the results from the following scales Mini Nutritional Assessment (MNA), Mini Mental State Examination (MMSE), anthropometric measurements for obtaining the body mass index (BMI) and biochemical analyses. The analyses were performed on the program SPSS version 20.0, using absolute and relative measures, T test for independent samples for measurement comparisons and the Spearman correlation test. In the cognitive evaluation MMSE, those participants with AD present higher risk of cognitive decline (81.8%), greater risk of malnutrition according to MNA (45.5%) and altered levels of leptin (90.9%). Upon performing the comparison analysis between the group with AD and the control group, there existed noteworthy differences between the means for the variables MNA (4.40; BMI95% 2.75 ­ 6.06), MMSE (10.54; BMI95% 7.09 ­ 13.99) and doses of HDL (High Density Lipoproteins) (14.53; BMI95% 6.18 ­ 22.88). As well as differences in the p-value < 0.09 in the leptin doses (11.54; BMI95% (-24.98 ­ 1.89) and transferrin dose (-72.31; BMI95% -159.48 ­ 14.84). The Spearman correlation demonstrated that the cognitive decline in the group of senior citizens with AD was strongly associated with nutritional conditions MNA (R 0.484) and the leptin dose (R 0.590). Senior citizens with AD present worse nutritional conditions, cognitive decline and biochemical alterations when compared to senior citizens in the control group. As such, the study demonstrated the need for an integrated healthcare assistance concerning senior citizens with AD.

Avaliar o estado nutricional e bioquímico de pacientes com Doença de Alzheimer (DA) comparando com um grupo controle. Materiais e métodos: trata-se de um tipo observacional, caso-controle e descritivo a partir do recrutamento de 22 idosos diagnosticados clinicamente com DA considerados grupo caso e outros 22 idosos considerados controle, foi utilizado a escala Mini Avaliação nutricional (MNA), Mini Exame do Estado Mental (MMSE), medidas antropométricas para obtenção do índice de massa corporal (IMC) e análises bioquímicas. As análises foram realizadas no programa SPSS versão 20.0, utilizou-se de medidas absolutas e relativas, teste T para amostras independentes para comparação de médias e o teste de correlação de Spearman. Na avaliação cognitiva MMSE os participantes com DA apresentaram maior prevalência de declínio cognitivo (81,8%), maior prevalência de risco para desnutrição segundo MNA (45,5%) e níveis alterados de leptina (90,9%). Ao se realizar a análise de comparação o grupo com DA e o controle observou-se diferenças significativas entre as médias das variáveis MNA (4,40; IC95% 2,75 ­ 6,06), MMSE (10,54; IC95% 7,09 ­ 13,99) e dosagens de HDL (14,53; IC95% 6,18 ­ 22,88). E diferenças com o p-valor < 0,09 nas dosagens de leptina (11,54; IC95% (-24,98 ­ 1,89) e dosagem de transferrina (-72,31; IC95% -159,48 ­ 14,84). A correlação de Spearman demonstrou que o declínio cognitivo no grupo de idosos com DA, esteve associado significativamente às condições nutricionais MNA (R 0,484) e dosagem de leptina (R 0,590). Idosos com DA apresentaram piores condições nutricionais, declínio cognitivo e alterações bioquímicas, ao compara-los com idosos controles. Desta forma, o estudo demonstra a necessidade de uma assistência integral a esses idosos.