Venous Thromboembolism Prophylaxis in Medical and Surgical Patients - What's Our Reality?

INTRODUCTION: Venous thromboembolism (VTE) includes pulmonary embolism (PE), deep vein thrombosis (DVT) in lower limbs, and thrombosis in rare locations. VTE is a common cardiovascular disease, being the leading preventable cause of in-hospital death. Both surgical and acute medical patients have an elevated risk of developing VTE. VTE risk assessment is essential to identify patients who might benefit from VTE prophylaxis accurately. Clinical data on risk factors and prophylaxis in Portugal are scarce. We aimed to determine the proportion of at-risk patients who received prophylaxis and the incidence of bleeding events. We also intended to study the rate of VTE in a cohort of medical and surgical patients during the hospitalization period and three months after discharge. METHODS: During one week in 2020, adults admitted for more than 72hr to a medical or surgical ward were included. The study excluded patients with a diagnosis of VTE three months before hospitalization and who were either chronically receiving anticoagulation therapy or had started it 48 hours after admission. Risk assessments were based on the Padua Prediction Score (PPS) for medical patients and the Caprini Risk Assessment Model (CRAM) for surgical patients. We used CHEST guidelines, 9th edition, to determine the adequacy of the prophylactic method. RESULTS: A total of 123 patients were analyzed, 18.7% of which tested positive for SARS-CoV-2. VTE risk in surgical patients was categorized as very low or low (16.6%), moderate (37.5%), and high (43.8%), according to the CRAM. Risk in medical patients was categorized as low (60.0%) or high (40.0%) according to the PPS. We estimated that VTE chemoprophylaxis was overused in about 30.0% of patients vs. 7.0% who were at risk and did not receive appropriate chemoprophylaxis. The rate of thromboembolic events was 4.1% (n=5), 2 of which happened after discharge. Two of these patients were under VTE prophylaxis during hospitalization. Major bleeding occurred in 2.4% of patients (n=3). DISCUSSION: A significant number of hospitalized patients are deemed to be at risk for VTE, making appropriate prophylaxis essential. The results emphasize the insufficient management of VTE prophylaxis.

Clinical Aspects and Etiologic Investigation of Pediatric Patients With Acute Liver Failure.

A new outbreak of hepatitis of unknown origin raised awareness in the international community. A few reports have attempted to associate new cases with adenovirus infection and the immunologic effects of previous SARS-CoV-2 infections through a superantigen mechanism. Moreover, according to a case series, viral isolates were identified in 7 of 10 cases of pediatric patients with hepatitis of unknown origin and acute liver failure. Adenovirus was detected by respiratory secretion polymerase chain reaction in 2 patients, with neither presenting with SARS-CoV-2 acute infection. Clinical and laboratory descriptions and cross-referencing epidemiologic and pathophysiological data can help identify possible disease etiologies.

Sarcomatoid Cholangiocarcinoma of the Common Bile Duct: An Unusual Entity.

Sarcomatous carcinoma of the bile duct is tremendously uncommon and aggressive. Herein, we report a case of a male who presented with jaundice. The thoraco-abdominopelvic tomography scan revealed a lesion within the common bile duct highly suspicious of malignancy. After laparoscopic pancreaticoduodenectomy, histological examination revealed a sarcomatous carcinoma. Two years after the initial diagnosis, the patient remains without signs of recurrence. Additional research about this rare condition is needed to improve care and prognosis.

Dietary-Induced Bacterial Metabolites Reduce Inflammation and Inflammation-Associated Cancer via Vitamin D Pathway.

Environmental factors, including westernised diets and alterations to the gut microbiota, are considered risk factors for inflammatory bowel diseases (IBD). The mechanisms underpinning diet-microbiota-host interactions are poorly understood in IBD. We present evidence that feeding a lard-based high-fat (HF) diet can protect mice from developing DSS-induced acute and chronic colitis and colitis-associated cancer (CAC) by significantly reducing tumour burden/incidence, immune cell infiltration, cytokine profile, and cell proliferation. We show that HF protection was associated with increased gut microbial diversity and a significant reduction in Proteobacteria and an increase in Firmicutes and Clostridium cluster XIVa abundance. Microbial functionality was modulated in terms of signalling fatty acids and bile acids (BA). Faecal secondary BAs were significantly induced to include moieties that can activate the vitamin D receptor (VDR), a nuclear receptor richly represented in the intestine and colon. Indeed, colonic VDR downstream target genes were upregulated in HF-fed mice and in combinatorial lipid-BAs-treated intestinal HT29 epithelial cells. Collectively, our data indicate that HF diet protects against colitis and CAC risk through gut microbiota and BA metabolites modulating vitamin D targeting pathways. Our data highlights the complex relationship between dietary fat-induced alterations of microbiota-host interactions in IBD/CAC pathophysiology.

Audiologist's Perspective in Auditory Rehabilitation: Implications for Ethical Conduct and Decision-Making in Portugal.

Ethical standards in audiology have been continuously improved and discussed, leading to the elaboration of specific regulatory guidelines for the profession. However, in the field of auditory rehabilitation, audiologists are still faced with circumstances that question their ethical principles, usually associated with the support of the hearing aids industry. The study explores the decision-making process and ethical concerns in auditory rehabilitation as they relate to the practice of audiology in Portugal. An online questionnaire constructed by the authors was used and sent to the email addresses of a list of audiologists, registered with the Portuguese Association of Audiologists. The questionnaire was answered by 93 audiologists with clinical experience in auditory rehabilitation for more than one year. The collected data demonstrated that audiometric results and clinical experience are the most important factors for decision-making in auditory rehabilitation practice. Moreover, incentives from the employers or manufacturers were identified as the main cause of ethical dilemmas. This study highlights the ethical concerns regarding the clinical practice of auditory rehabilitation in Portugal, revealing that the decision-making process is complex and, specifically in this field, the current practice may not be adequate for effective compliance with professional ethical standards.

Asymmetric sensorineural hearing loss in children: progression and involvement of the contralateral ear.

BACKGROUND: Sensorineural hearing loss in child has a profound impact on their neurodevelopment and on language acquisition. Thus, the diagnosis and early intervention are critical, namely in unilateral or bilateral asymmetric hearing losses, which are diagnosed later than symmetric bilateral hearing losses. OBJECTIVES: This study aims to examine the progression of asymmetric SNHL in children, and the link between hearing thresholds and the technological level of the hearing aid fitted. MATERIAL AND METHODS: Eighteen children with asymmetric SNHL were submitted to a pure tone audiogram at the age of 5 years (T0) and reassessed at the age of 10 years (T1). Children were divided according to the technological level of the hearing aid fitted: basic, medium, and advanced. RESULTS: A positive correlation was established between the hearing thresholds at T0 and T1, revealing an accelerated progression of hearing thresholds in the better ear after a 5-year period. CONCLUSIONS: Hearing thresholds in the worse ear influence the progression of the SNHL. Moreover, technologically advanced hearing aids led to a slower progression of the hearing thresholds over time.

Age-related hearing loss, depression and auditory amplification: a randomized clinical trial.

PURPOSE: Our study investigates the effectiveness of aural rehabilitation to decrease depressive symptoms in older adults, and the relationship between hearing loss and depression. METHODS: A randomized controlled study was conducted at a hearing rehabilitation center with people over 65 years old. Participants were randomly allocated to the intervention group who received hearing aids, or to the control group. Data collection included pure-tone audiometry and a Portuguese version of the Geriatric Depression Scale assessed at two time points: baseline (P0) and after 4-week period (P1). RESULTS: The results show that the increase of hearing thresholds in pure-tone audiometry is associated with a significant increase in depressive symptoms (p = 0.001). The effect of aural rehabilitation for improving depressive symptoms was significant in intervention group (p = 0.000) and between groups (p = 0.003) in P1. CONCLUSION: Age-related hearing loss has adverse effects on older adults' mental health, due to reduced hearing inputs that may increase levels of effort to communicate and affect social engagement, which lead to depression. Hearing aid use improves levels of depression and can promote greater quality of life in older adults.

Repercussions of the COVID-19 pandemic on breast cancer treatment in a referral hospital in Santos-SP, Brazil

Objective: Considering that breast cancer has the fifth highest mortality rate in the world, this study aims to evaluate the repercussions of the COVID-19 pandemic on the treatment, both surgical and systemic, of patients with cancer in general and those with breast cancer at Hospital Guilherme Álvaro (Santos, Brazil), between March 1st, 2019 and February 28, 2021. Methods: For this purpose, data were collected from both the hospital's surgery record book and electronic medical records of patients who were followed up in the Mastology and Oncology sectors at Hospital Guilherme Álvaro. This information was tabulated, estimating the total number of surgeries, whether: benign elective surgeries, diagnostic surgeries, surgeries of cancer in general, surgeries exclusive to mastology, of cancer in mastology, benign surgery in mastology, and plastic reconstructive surgery. The percentage ratio between these numbers was calculated. Results: A 49% reduction in total surgeries was observed, comparing the period prior to the pandemic (2019­2020) with the pandemic period (2020­2021), with a decrease of 24.6% in the number of general cancer surgeries except for mastology, and 19.6% of surgeries exclusive to mastology. In other words, there was a total reduction of 22.9% in all oncological surgeries. Moreover, there was a decrease of 11.5% in the total number of patients treated with chemotherapy. In 2020, of the 214 new cases, 116 (54.2%) were mastology patients, being 45.8% of other oncology clinics. Conclusion: Thus, it is concluded that the reduction in the number of aesthetic, benign, and reconstructive surgeries was expected, as observed in the decrease in the number of chemotherapies, which could be due to a limitation on medical appointments. The number of diagnostic surgeries remained stable, which could lead to positive outcomes for oncology patients. It is not possible to predict the next repercussions of the COVID-19 pandemic on breast cancer treatment while the pandemic endures, requiring more studies on this topic.

Acute Effects of Butyrate on Induced Hyperpermeability and Tight Junction Protein Expression in Human Colonic Tissues.

Intact intestinal barrier function is essential for maintaining intestinal homeostasis. A dysfunctional intestinal barrier can lead to local and systemic inflammation through translocation of luminal antigens and has been associated with a range of health disorders. Butyrate, a short-chain fatty acid derived from microbial fermentation of dietary fibers in the colon, has been described as an intestinal barrier-strengthening agent, although mainly by using in vitro and animal models. This study aimed to investigate butyrate's ability to prevent intestinal hyperpermeability, induced by the mast cell degranulator Compound 48/80 (C48/80), in human colonic tissues. Colonic biopsies were collected from 16 healthy subjects and intestinal permeability was assessed by Ussing chamber experiments. Furthermore, the expression levels of tight junction-related proteins were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Pre-treatment with 5 mM butyrate or 25 mM butyrate did not protect the colonic tissue against induced paracellular or transcellular hyperpermeability, measured by FITC-dextran and horseradish peroxidase passage, respectively. Biopsies treated with 25 mM butyrate prior to stimulation with C48/80 showed a reduced expression of claudin 1. In conclusion, this translational ex vivo study did not demonstrate an acute protective effect of butyrate against a chemical insult to the intestinal barrier in healthy humans.

Qualitative modelling of the interplay of inflammatory status and butyrate in the human gut: a hypotheses about robust bi-stability.

BACKGROUND: Gut microbiota interacts with the human gut in multiple ways. Microbiota composition is altered in inflamed gut conditions. Likewise, certain microbial fermentation products as well as the lipopolysaccharides of the outer membrane are examples of microbial products with opposing influences on gut epithelium inflammation status. This system of intricate interactions is known to play a core role in human gut inflammatory diseases. Here, we present and analyse a simplified model of bidirectional interaction between the microbiota and the host: in focus is butyrate as an example for a bacterial fermentation product with anti-inflammatory properties. RESULTS: We build a dynamical model based on an existing model of inflammatory regulation in gut epithelial cells. Our model introduces both butyrate as a bacterial product which counteracts inflammation, as well as bacterial LPS as a pro-inflammatory bacterial product. Moreover, we propose an extension of this model that also includes a feedback interaction towards bacterial composition. The analysis of these dynamical models shows robust bi-stability driven by butyrate concentrations in the gut. The extended model hints towards a further possible enforcement of the observed bi-stability via alteration of gut bacterial composition. A theoretical perspective on the stability of the described switch-like character is discussed. CONCLUSIONS: Interpreting the results of this qualitative model allows formulating hypotheses about the switch-like character of inflammatory regulation in the gut epithelium, involving bacterial products as constitutive parts of the system. We also speculate about possible explanations for observed bimodal distributions in bacterial compositions in the human gut. The switch-like behaviour of the system proved to be mostly independent of parameter choices. Further implications of the qualitative character of our modeling approach for the robustness of the proposed hypotheses are discussed, as well as the pronounced role of butyrate compared to other inflammatory regulators, especially LPS, NF- κB and cytokines.

Pseudomyxoma peritonei originating from appendix tumors / Pseudomixoma peritoneal com origem em tumores do apêndice

ABSTRACT Background: Appendix tumors represent about 1% of all gastrointestinal neoplasia, in other words they are quite rare. However, there is a specific type of appendiceal neoplasms (mucinous adenocarcinoma) that spreads to the peritoneum and in almost 20% of the cases, resulting in a disease called pseudomyxoma peritonei. Although, it is a very rare condition, it is nonetheless a very severe one and therefore it is crucial to know how to correctly diagnose and treat it. Objective: This study provides updated data on how to diagnose, classify and treat pseudomyxoma peritonei that originates from appendix tumors. Methods: A bibliographic research was performed on PubMed database, including articles published since 2000, as well as, cross-referencing with the initial research. Discussion: In the past, patients diagnosed with pseudomyxoma peritonei would only undergo palliative measures, so their overall survival rate was greatly reduced. Over the years pseudomyxoma peritonei treatment has evolved and patients are now undergoing treatment which is a combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. This new therapy has allowed an increase of survival chances of up to 5 years in those patients with values between 53% and 88%, depending on the type of tumor. Conclusion: Despite the great progress we have witnessed in recent years, which have led to a large increase in survival rates, more research needs to be done, on what to do when the disease is in an unresectable stage. Finding a less aggressive therapy than cytoreductive surgery + hyperthermic intraperitoneal chemotherapy will be an important step forward.

RESUMO Introdução: As neoplasias do apêndice são bastante raras, representando atualmente cerca de 1% de todas as neoplasias gastrointestinais. O adenocarcinoma mucinoso é um dos subtipos de neoplasia do apêndice e caracteriza-se por metastizar para o peritoneu, em 20% dos casos, facto que se manifesta sob a forma de uma doença designada por Pseudomixoma Peritoneal. Apesar de ser uma condição muito rara, a sua extrema gravidade justifica a importância de a saber diagnosticar e tratar corretamente. Métodos: Foi realizada uma pesquisa bibliográfica na base de dados PubMed, incluindo artigos publicados desde 2000 bem como artigos de pesquisa cruzada com os iniciais. Discussão: No passado, os doentes diagnosticados com Pseudomixoma Peritoneal eram apenas submetidos a medidas paliativas, pelo que a sua sobrevida era muito reduzida. Ao longo dos anos o tratamento do Pseudomixoma Peritoneal foi evoluindo sendo agora os doentes submetidos a uma combinação de cirurgia citoredutiva e quimioterapia hipertérmica intraperitoneal. Esta nova terapêutica tem permitido aumentar a sobrevida aos 5 anos destes pacientes para valores entre os 53% e os 88%, dependendo do tipo de tumor. Conclusões: Apesar dos grandes avanços que se têm verificado, e que culminaram com um grande aumento das taxas de sobrevivência, devem ser feitos mais estudos que encontrem novas abordagens para quando o tumor já é diagnosticado num estado irressecável, bem como terapêuticas menos invasivas.

Development and characterization of a nanoemulsion containing propranolol for topical delivery.

BACKGROUND: Propranolol (PPN) is a therapeutic option for the treatment of infantile hemangiomas. This study aimed at the development of nanoemulsion (NE) containing 1% PPN, characterization of the system, and safety studies based on ex vivo permeation, cytotoxicity, and biodistribution in vivo. METHODS: The formulation was developed and characterized in relation to the droplet size, polydispersity index (PDI), pH, zeta potential, and electronic microscopy. Ex vivo permeation studies were used to evaluate the cutaneous retention of PPN in the epidermis and dermis. Cytotoxicity studies were performed in fibroblasts, macrophages, and keratinocytes. In vivo biodistribution assay of the formulations was performed by means of labeling with technetium-99m. RESULTS: NE1 exhibited droplet size of 26 nm, PDI <0.4, pH compatible with the skin, and zeta potential of -20 mV, which possibly contributes to the stability. Electron microscopy showed that the NE presented droplets of nanometric size and spherical shape. NE1 provided excellent stability for PPN. In the ex vivo cutaneous permeation assay, the NE provided satisfactory PPN retention particularly in the dermis, which is the site of drug action. In addition, NE1 promoted cutaneous permeation of the PPN in small amount. In vivo biodistribution showed that the radiolabeled formulation remained in the skin and a small amount reached the bloodstream. NE1 presented low cytotoxicity to fibroblasts, macrophages, and keratinocytes in the concentrations evaluated in the cytotoxicity assay. CONCLUSION: We concluded that the formulation is safe for skin administration; however, cutaneous irritation studies should be performed to confirm the safety of the formulation before clinical studies in patients with infantile hemangiomas.

Surgical Treatment of Facial Infantile Hemangiomas: An Analysis Based on Tumor Characteristics and Outcomes.

BACKGROUND: Surgical treatment of infantile hemangiomas may interfere with patient appearance. The use of an algorithm is essential to select candidates. The objective of this study was to evaluate outcomes of surgical treatment based on tumor characteristics. METHODS: Seventy-four patients were treated surgically between 1997 and 2010. Demographics, tumor characteristics, surgical approach, and outcomes were evaluated. RESULTS: The female-to-male ratio was 5.7:1. Mean age and follow-up were 24 years and 33 months, respectively. Surgery was elective in 83.8 percent and emergent in 16.2 percent of patients. Most frequent locations were lips, nose, eyelids, and cheeks. Surgery was performed during the proliferative phase in 43 patients (58.1 percent), and growth-related deformity was the main indication. No significant association between sex and the presence of complications or treatment indication was observed. Patients who underwent emergency procedures were younger (p = 0.0031) and had a higher incidence of evolutional complications (p = 0.012). Also, they were more frequently operated on during the proliferative phase (p = 0.011). Favorable outcome of surgical treatment was observed in both simple and complex cases for facial contour, volume reduction, and need for reoperation. The best candidates for elective surgery were patients with localized eyelid, nasal, or lip hemangiomas, presenting growth-related deformities during the proliferative phase. For patients undergoing emergency procedures, the best candidates were nonresponders to pharmacologic therapy with segmental periorbital hemangiomas, treated by partial resection. CONCLUSIONS: A profile of patients and their specific surgical approach was established. Satisfactory results could be achieved following the proposed algorithm. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Determinação do perfil fitoquímico e avaliação das atividades biológicas de extrato da espécie Scleronema micranthum da família Bombacaceae / Determination of the phytochemical profile and evaluation of biological activities of extract of species Scleronema micranthum in the Bombacaceae family

As plantas medicinais são usadas desde a antiguidade para tratar diversas doenças e, têm subsidiado a pesquisa farmacêutica na descoberta de novos agentes biologicamente ativos. Neste contexto, foi realizada a prospecção fitoquímica, a avaliação das atividades citotóxica, antimicrobiana e antioxidante do extrato etanólico obtido das folhas da espécie Scleronema micranthum Ducke (Bombacaceae), conhecida popularmente como cedrinho. Os resultados obtidos na prospecção fitoquímica sugerem a presença dos componentes metabólicos leucoantocianidinas, flavonoides, saponinas e fenóis. As moderadas atividades citotóxica e antioxidante estabelecidas para o extrato bruto, podem despertar o interesse das empresas farmacêuticas em razão da pesquisa por novos agentes antitumorais e anti-inflamatórios oriundos da Floresta Amazônica. Deste modo, os resultados obtidos neste estudo representam uma clara oportunidade para gerar benefícios econômicos e estimular a competitividade da indústria farmacêutica nacional, a partir da prospecção de novos agentes bioativos aplicados ao controle de doenças de importância para a saúde pública.(AU)

Medicinal plants are used since ancient times to treat various diseases and have subsidized pharmaceutical research in the discovery of new biologically active agents. In this context, we evaluated the phytochemical prospection, the cytotoxicity, antimicrobial and antioxidant activities of the ethanolic extract obtained from the leaves of the species Scleronema micranthum Ducke (Bombacaceae), popularly known as "cedrinho". The results achieved in this phytochemical prospection suggest the presence of leucoanthocyanidins, flavonoids, saponins and phenols, as metabolic components. The moderate cytotoxic and antioxidant activities of the crude extract can arouse the interest of pharmaceutical companies in search of new antitumor and anti-inflammatory agents derived from the Amazon Rainforest. We hope the results obtained in this study indicates a clear opportunity of generating economic benefits and boosting the competitiveness of the national pharmaceutical industry, prospecting new bioactive agents to control diseases of public health importance.(AU)

The relationship between socioeconomic indicators during pregnancy and gynecological appointment at any time after childbirth.

BACKGROUND: The rates of receipt of postnatal care vary widely between high and low-middle income countries. This study aimed to examine the association between indicators of socioeconomic status during pregnancy and gynecological appointment at any time after childbirth (GA). METHODS: a prospective cohort study with pregnant women recruited from 10 primary care clinics of the public sector in the city of São Paulo, Brazil. Socioeconomic characteristics and obstetric information were obtained through a questionnaire administered during pregnancy and in the postpartum period. Adjusted risk ratios (RR) with 95% confidence intervals (CI) were calculated using Poisson regression. RESULTS: Eight hundred and thirty one pregnant women were included in the study during the antenatal period and 701 were re-assessed during the postnatal period. Among them, 283 (59.6) attended a gynecological consultation. After adjusting for covariates, higher socioeconomic status during pregnancy was associated with greater risk of having a GA (RR:1.23, CI 95%:1.05:1.45 for family per capita monthly income; RR:1.19, CI 95 % 1.01:1.40 for asset score). CONCLUSION: In this sample, the attendance for GA was above average and women with higher socio-economic status were more likely to have receipt of such care. Special efforts should be made to improve the attendance and frequency of gynecological consultations after childbirth among poorer women.

Dietary trans-10, cis-12-conjugated linoleic acid alters fatty acid metabolism and microbiota composition in mice.

The main aim of the present study was to investigate the effects of dietary trans-10, cis-12-conjugated linoleic acid (t10c12-CLA) on intestinal microbiota composition and SCFA production. C57BL/6 mice (n 8 per group) were fed a standard diet either supplemented with t10c12-CLA (0·5 %, w/w) (intervention) or with no supplementation (control), daily for 8 weeks. Metabolic markers (serum glucose, leptin, insulin and TAG, and liver TAG) were assessed by ELISA commercial kits, tissue long-chain fatty acids and caecal SCFA by GC, and microbial composition by 16S rRNA pyrosequencing. Dietary t10c12-CLA significantly decreased visceral fat mass (P< 0·001), but did not affect body weight (intervention), when compared with no supplementation (control). Additionally, lipid mass and composition were affected by t10c12-CLA intake. Caecal acetate, propionate and isobutyrate concentrations were higher (P< 0·05) in the t10c12-CLA-supplemented group than in the control group. The analysis of the microbiota composition following 8 weeks of t10c12-CLA supplementation revealed lower proportions of Firmicutes (P= 0·003) and higher proportions of Bacteroidetes (P= 0·027) compared with no supplementation. Furthermore, t10c12-CLA supplementation for 8 weeks significantly altered the gut microbiota composition, harbouring higher proportions of Bacteroidetes, including Porphyromonadaceae bacteria previously linked with negative effects on lipid metabolism and induction of hepatic steatosis. These results indicate that the mechanism of dietary t10c12-CLA on lipid metabolism in mice may be, at least, partially mediated by alterations in gut microbiota composition and functionality.

Surgical treatment of extracranial arteriovenous malformations after multiple embolizations: outcomes in a series of 31 patients.

BACKGROUND: Surgical resection after embolization is the most accepted approach to treating arteriovenous malformations. The authors analyzed the outcome of surgically treated patients and how surgical resection was influenced by multiple embolizations. METHODS: Thirty-one patients were included from January of 2000 to December of 2012. The mean patient age was 24.9 years. Anatomical involvement, definition of limits, functional impairment, number of embolizations, type of resection, reconstruction method, blood transfusion, and hospital stay were evaluated. Morbidity, mortality, and regrowth rates and need for additional procedures were evaluated. RESULTS: Lesions were preferentially located at the orbits, cheeks, and lips. The number of embolizations per patient increased with lesion complexity. In 22 cases, total excision was accomplished, and in nine, subtotal resections were performed to favor function. After multiple embolizations, better lesion identification was observed. Primary closure was performed in 20 cases, local flaps were performed in seven cases, axial flaps were performed in two patients, and free flaps were performed in two cases. There were no deaths. Regrowth rates were influenced by limits between arteriovenous malformations and surrounding tissues (15.8 percent of cases with precise limits versus 58.3 percent of lesions with imprecise limits; p = 0.021) and by type of resection (18.2 percent of cases after total resection versus 66.7 percent after subtotal resections; p = 0.015). CONCLUSIONS: Multiple therapeutic embolizations seem to increase safety in the treatment of arteriovenous vascular malformations and suggest an additional positive effect besides bleeding control. Preoperative definition of limits and establishment of conditions for total resection are critical to determine management and risk of regrowth. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Streptozotocin-induced type-1-diabetes disease onset in Sprague-Dawley rats is associated with an altered intestinal microbiota composition and decreased diversity.

There is a growing appreciation that microbiota composition can significantly affect host health and play a role in disease onset and progression. This study assessed the impact of streptozotocin (STZ)-induced type-1-diabetes (T1D) on intestinal microbiota composition and diversity in Sprague-Dawley rats, compared with healthy controls over time. T1D was induced by injection of a single dose (60 mg STZ kg(-1)) of STZ, administered via the intraperitoneal cavity. Total DNA was isolated from faecal pellets at weeks 0 (pre-STZ injection), 1, 2 and 4 and from caecal content at week 5 from both healthy and T1D groups. High-throughput 16S rRNA sequencing was employed to investigate intestinal microbiota composition. The data revealed that although intestinal microbiota composition between the groups was similar at week 0, a dramatic impact of T1D development on the microbiota was apparent post-STZ injection and for up to 5 weeks. Most notably, T1D onset was associated with a shift in the Bacteroidetes : Firmicutes ratio (P<0.05), while at the genus level, increased proportions of lactic acid producing bacteria such as Lactobacillus and Bifidobacterium were associated with the later stages of T1D progression (P<0.05). Coincidently, T1D increased caecal lactate levels (P<0.05). Microbial diversity was also reduced following T1D (P<0.05). Principle co-ordinate analyses demonstrated temporal clustering in T1D and control groups with distinct separation between groups. The results provide a comprehensive account of how T1D is associated with an altered intestinal microbiota composition and reduced microbial diversity over time.

Divergent metabolic outcomes arising from targeted manipulation of the gut microbiota in diet-induced obesity.

OBJECTIVE: The gut microbiota is an environmental regulator of fat storage and adiposity. Whether the microbiota represents a realistic therapeutic target for improving metabolic health is unclear. This study explored two antimicrobial strategies for their impact on metabolic abnormalities in murine diet-induced obesity: oral vancomycin and a bacteriocin-producing probiotic (Lactobacillus salivarius UCC118 Bac(+)). DESIGN: Male (7-week-old) C57BL/J6 mice (9-10/group) were fed a low-fat (lean) or a high-fat diet for 20 weeks with/without vancomycin by gavage at 2 mg/day, or with L. salivarius UCC118Bac(+) or the bacteriocin-negative derivative L. salivarius UCC118Bac(-) (each at a dose of 1×10(9) cfu/day by gavage). Compositional analysis of the microbiota was by 16S rDNA amplicon pyrosequencing. RESULTS: Analysis of the gut microbiota showed that vancomycin treatment led to significant reductions in the proportions of Firmicutes and Bacteroidetes and a dramatic increase in Proteobacteria, with no change in Actinobacteria. Vancomycin-treated high-fat-fed mice gained less weight over the intervention period despite similar caloric intake, and had lower fasting blood glucose, plasma TNFα and triglyceride levels compared with diet-induced obese controls. The bacteriocin-producing probiotic had no significant impact on the proportions of Firmicutes but resulted in a relative increase in Bacteroidetes and Proteobacteria and a decrease in Actinobacteria compared with the non-bacteriocin-producing control. No improvement in metabolic profiles was observed in probiotic-fed diet-induced obese mice. CONCLUSION: Both vancomycin and the bacteriocin-producing probiotic altered the gut microbiota in diet-induced obese mice, but in distinct ways. Only vancomycin treatment resulted in an improvement in the metabolic abnormalities associated with obesity thereby establishing that while the gut microbiota is a realistic therapeutic target, the specificity of the antimicrobial agent employed is critical.

Antimicrobials: Strategies for targeting obesity and metabolic health?

Obesity is associated with a number of serious health consequences, including type 2 diabetes, cardiovascular disease and a variety of cancers among others and has been repeatedly shown to be associated with a higher risk of mortality. The relatively recent discovery that the composition and metabolic activity of the gut microbiota may affect the risk of developing obesity and related disorders has led to an explosion of interest in this distinct research field. A corollary of these findings would suggest that modulation of gut microbial populations can have beneficial effects with respect to controlling obesity. In this addendum, we summarize our recent data, showing that therapeutic manipulation of the microbiota using different antimicrobial strategies may be a useful approach for the management of obesity and metabolic conditions. In addition, we will explore some of the mechanisms that may contribute to microbiota-induced susceptibility to obesity and metabolic diseases.