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.

COMBINSI (COMBat to INSufficient Insulin therapy) - A Portuguese project in type 2 diabetes.

BACKGROUND: Inadequate glycemic control in type 2 diabetes (T2D) increases the risk of diabetes-related complications. Insulin initiation is often delayed for several years. This study aims to estimate the adequacy of insulin therapy prescription to people living with T2D in a primary care setting. MATERIAL AND METHODS: This was a cross-sectional study based on adults with T2D in a Portuguese local health unit between January 2019 and January 2020. Subjects under insulin therapy were compared with non-insulin-treated subjects with Hemoglobin A1c (HbA1c) ≥9% regarding clinical and demographic characteristics. The proportion of insulin-treated subjects in both of these groups was defined as insulin therapy index. RESULTS: Our study included 13,869 adults living with T2D, among whom 11.5% were treated with insulin therapy and 4.1% had HbA1c ≥ 9% and were not under insulin therapy. Insulin therapy index was 73.9%. When comparing with non-insulin-treated subjects with HbA1c ≥ 9%, insulin-treated subjects were significantly older (75.8 vs 66.2 years p < 0.001), had lower HbA1c (8.3 vs 10.3% p < 0.001), lower estimated glomerular filtration rate (66.4 vs 74.0 ml/min/1.73 m2p < 0.001), lower LDL-cholesterol (87.1 vs 105.8 mg/dl), and higher rates of atherosclerotic cardiovascular disease (32.7 vs 16.7% p < 0.001). CONCLUSION: Insulin therapy is underprescribed in T2D, with over 1-in-4 people living with T2D not being prescribed insulin despite deficient glycemic control. These findings highlight the need for insulin therapy when glycemic control is inadequate under other interventions.

Underprescription of SGLT2i and GLP-1 RA: CAREPRO-T2D (Cardiorenal Protection in Type 2 Diabetes) Cross-Sectional Study.

BACKGROUND: New glucose-lowering drugs have shown benefits regarding cardiovascular events, heart failure, and kidney-related outcomes in type 2 diabetes (T2D). This study aimed to estimate the adequacy of SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1 RA) prescription to people living with T2D with established atherosclerotic cardiovascular disease (ASCVD) or heart failure (HF). MATERIAL AND METHODS: This was a cross-sectional study based on adults with T2D in a Portuguese local health unit between January 2019 and January 2020. Subjects with ASCVD were compared with subjects without ASCVD, and subjects with HF were compared with subjects without HF regarding clinical and demographic characteristics. RESULTS: Our study included 13,869 adults with T2D, among whom 5.9% were coded for HF and 20.4% were defined as having ASCVD. SGLT2i were prescribed to 36.0% of subjects with HF. SGLT2i and/or GLP-1 RA were prescribed to 36.1% of patients with ASCVD. When comparing with subjects without ASCVD, subjects with ASCVD were significantly older (70.8 vs. 66.5 years, p<0.001), had lower estimated glomerular filtration rate (68.2 vs. 74.6 mL/min/1.73 m2, p<0.001), and higher rates of prescription of SGLT2i and/or GLP-1 RA (36.1 vs. 31.4%, p<0.001). When comparing with subjects without HF, subjects with HF were significantly older (74.6 vs. 66.9 years, p<0.001), had lower estimated glomerular filtration rate (59.6 vs. 74.1, mL/min/1.73 m2, p<0.001), and higher rates of prescription of SGLT2i (36.0 vs. 30.3%, p<0.001). CONCLUSION: SGLT2i and GLP-1 RA are underprescribed in T2D, with almost two-thirds of patients not being prescribed these agents despite being strongly advised by current guidelines. These findings highlight the need for specific actions to improve T2D management at primary care level.

Lipidomic Characterization and Antioxidant Activity of Macro- and Microalgae Blend.

Macro- and microalgae are currently recognized sources of lipids with great nutritional quality and attractive bioactivities for human health promotion and disease prevention. Due to the lipidomic diversity observed among algae species, giving rise to different nutritional and functional characteristics, the mixture of macro- and microalgae has the potential to present important synergistic effects resulting from the complementarity among algae. The aim of this work was to characterize for the first time the lipidome of a blend of macro- and microalgae and evaluate the antioxidant capacity of its lipid fraction. Fatty acids were profiled by GC-MS, the polar lipidome was identified by high resolution LC-MS, and ABTS+• and DPPH• assays were used to assess the antioxidant potential. The most abundant fatty acids were oleic (18:1 n-9), α-linolenic (18:3 n-3), and linoleic (18:2 n-6) acids. The lipid extract presented a beneficial n-6/n-3 ratio (0.98) and low values of atherogenic (0.41) and thrombogenic indices (0.27). The polar lipidome revealed 462 lipid species distributed by glycolipids, phospholipids, and betaine lipids, including some species bearing PUFA and a few with reported bioactivities. The lipid extract also showed antioxidant activity. Overall, the results are promising for the valorization of this blend for food, nutraceutical, and biotechnological applications.

Applications of lipidomics in marine organisms: progress, challenges and future perspectives.

Marine ecosystems comprise a high diversity of life forms, such as algae, invertebrates, and vertebrates. These organisms have adapted their physiology according to the conditions of the environments in which they inhabit. In the last few years, the study of lipids of marine origin has received increasing attention due to the diversity of their composition. The progress of analytical techniques such as LC-MS and MS/MS has allowed researchers to improve accurate processing of samples and lipid characterization. Lipidomics is a useful research field to understand marine ecosystems and the physiology of their organisms. The screening of biological systems in marine environments has demonstrated a significant diversity of lipids in their living resources. In this review, we provide the state-of-the-art marine of lipidomics studies. We describe in detail the lipidomics approach for the analysis of marine lipidomes, including sample collection and preparation, interpretation of MS/MS fragmentation fingerprinting, data analysis and processing. Special attention is also given to illustrate the latest applications and advances of applied LC-MS lipidomic analyses in diversified studies of different marine organisms, as well as the challenges and future perspectives of marine lipidomics.

COVID-19 pandemic impact on cytopathology practice in the post-lockdown period: An international, multicenter study.

BACKGROUND: In a previous worldwide survey, the authors showed a drastic reduction in the number of cytological specimens processed during the coronavirus disease 2019 "lockdown" period along with an increase in malignancy rates. To assess the continued impact of the pandemic on cytological practices around the world, they undertook a second follow-up worldwide survey collecting data from the post-lockdown period (2020). METHODS: Participants were asked to provide data regarding their cytopathology activity during the first 12 weeks of their respective national post-lockdown period (2020), which ranged from April 4 to October 31. Differences between the post-lockdown period and the corresponding 2019 period were evaluated, and the authors specifically focused on rates of malignant diagnoses. RESULTS: A total of 29 respondents from 17 countries worldwide joined the survey. Overall, a lower number of cytological specimens (n = 236,352) were processed in comparison with the same period in 2019 (n = 321,466) for a relative reduction of 26.5%. The overall malignancy rate showed a statistically significant increase (12,442 [5.26%] vs 12,882 [4.01%]; P < .001) during the same time period. Similar results were obtained if both malignancy and suspicious for malignancy rates were considered together (15,759 [6.58%] vs 16,011 [4.98%]; P < .001). CONCLUSIONS: The data showed a persistent reduction in the cytological specimen volume during the post-lockdown period (2020). However, the relative increase in the cytological workload in the late part of the post-lockdown is a promising finding of a slow return to normality.

Seaweed Blends as a Valuable Source of Polyunsaturated and Healthy Fats for Nutritional and Food Applications.

Seaweeds are considered healthy and sustainable food. Although their consumption is modest in Western countries, the demand for seaweed in food markets is increasing in Europe. Each seaweed species has unique nutritional and functional features. The preparation of blends, obtained by mixing several seaweeds species, allows the obtaining of maximum benefits and ingredients with single characteristics. In this work, five seaweed blends, commercially available and produced under organic conditions in Europe, were characterized. The proximal composition included contents of ash (20.28-28.68% DW), proteins (17.79-26.61% DW), lipids (0.55-1.50% DW), and total carbohydrates (39.47-47.37% DW). Fatty acid profiles were determined by gas chromatography-mass spectrometry (GC-MS), allowing quantification of healthy fatty acids, namely n-3 and n-6 polyunsaturated fatty acids (PUFA), and calculation of lipid quality indices. Each blend showed a characteristic PUFA content in the lipid pool (35.77-49.43% of total fatty acids) and the content in essential and healthy n-3 PUFA is highlighted. The atherogenicity (0.54-0.72) and thrombogenicity (0.23-0.45) indices evidenced a good nutritional value of lipid fractions. As nutritional and environmentally attractive products, the consumption of the studied seaweed blends can contribute to a healthy lifestyle.

Intensive calcium monitoring improves outcomes on hungry bone syndrome in hyperparathyroidism.

Objectives. Hungry bone syndrome (HBS) is a severe and underdiagnosed complication of parathyroidectomy in the treatment of primary hyperparathyroidism (PHP) and secondary hyper-parathyroidism to chronic kidney disease (SHP-CKD).Methods. A longitudinal study was conducted to compare the postoperative outcomes of patients who developed HBS in two different time frames: before and after implementing a protocol with an intensive electrolytic monitoring and an algorithm regarding electrolytic supplementation.Results. Overall, 77 parathyroidectomies were included. In PHP, a protocol implementation led to an increased admission of patients in the Intermediate Care Unit for intensive electrolytic monitoring (p<0.001) and an increased rate of oral calcium replacement during hospital stay (p=0.013) compared to pre-protocol era. In SHP-CKD, duration of intravenous calcium replacement was reduced (p=0.010). The prevalence of HBS (9.8% in PHP and 58.3% in SHP-CKD) was similar between the two periods, although its diagnosis had an increased trend in PHP since the protocol implementation. None of the diagnosis of HBS was established due to hypocalcemic symptoms in the post-protocol era (contrary to pre-protocol period, p=0.021). Both hypocalcemia length and duration of surgical ward hospitalization were reduced (p=0.047 and p=0.042, respectively).Conclusions. An improved assessment of hyperparathyroidism and a decrease in HBS severity were noted in the post-protocol era. We strongly recommend the implementation of a standardized protocol with an intensive phosphocalcium monitoring in the high-risk patients who undergo parathyroidectomy due to hyperparathyroidism as it improves the health care and management of HBS.

Global impact of the COVID-19 pandemic on cytopathology practice: Results from an international survey of laboratories in 23 countries.

BACKGROUND: To the authors' knowledge, the impact of the coronavirus disease 2019 (COVID-19) pandemic on cytopathology practices worldwide has not been investigated formally. In the current study, data from 41 respondents from 23 countries were reported. METHODS: Data regarding the activity of each cytopathology laboratory during 4 weeks of COVID-19 lockdown were collected and compared with those obtained during the corresponding period in 2019. The overall number and percentage of exfoliative and fine-needle aspiration cytology samples from each anatomic site were recorded. Differences in the malignancy and suspicious rates between the 2 periods were analyzed using a meta-analytical approach. RESULTS: Overall, the sample volume was lower compared with 2019 (104,319 samples vs 190,225 samples), with an average volume reduction of 45.3% (range, 0.1%-98.0%). The percentage of samples from the cervicovaginal tract, thyroid, and anorectal region was significantly reduced (P < .05). Conversely, the percentage of samples from the urinary tract, serous cavities, breast, lymph nodes, respiratory tract, salivary glands, central nervous system, gastrointestinal tract, pancreas, liver, and biliary tract increased (P < .05). An overall increase of 5.56% (95% CI, 3.77%-7.35%) in the malignancy rate in nongynecological samples during the COVID-19 pandemic was observed. When the suspicious category was included, the overall increase was 6.95% (95% CI, 4.63%-9.27%). CONCLUSIONS: The COVID-19 pandemic resulted in a drastic reduction in the total number of cytology specimens regardless of anatomic site or specimen type. The rate of malignancy increased, reflecting the prioritization of patients with cancer who were considered to be at high risk. Prospective monitoring of the effect of delays in access to health services during the lockdown period is warranted.

Terpinen-4-ol, tyrosol, and ß-lapachone as potential antifungals against dimorphic fungi

Abstract This study aimed to evaluate the in vitro antifungal activity of terpinen-4-ol, tyrosol, and β-lapachone against strains of Coccidioides posadasii in filamentous phase (n = 22) and Histoplasma capsulatum in both filamentous (n = 40) and yeast phases (n = 13), using the broth dilution methods as described by the Clinical and Laboratory Standards Institute, to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of these compounds. The mechanisms of action of these compounds were also investigated by analyzing their effect on cell membrane permeability and ergosterol synthesis. The MIC and MFCf these compounds against C. posadasii, mycelial H. capsulatum, and yeast-like H. capsulatum, were in the following ranges: 350-5720 µg/mL, 20-2860 µg/mL, and 40-1420 µg/mL, respectively for terpinen-4-ol; 250-4000 µg/mL, 30-2000 µg/mL, and 10-1000 µg/mL, respectively, for tyrosol; and 0.48-7.8 µg/mL, 0.25-16 µg/mL, and 0.125-4 µg/mL, respectively for β-lapachone. These compounds showed a decrease in MIC when the samples were subjected to osmotic stress, suggesting that the compounds acted on the fungal membrane. All the compounds were able to reduce the ergosterol content of the fungal strains. Finally, tyrosol was able to cause a leakage of intracellular molecules.

Terpinen-4-ol, tyrosol, and ß-lapachone as potential antifungals against dimorphic fungi.

This study aimed to evaluate the in vitro antifungal activity of terpinen-4-ol, tyrosol, and ß-lapachone against strains of Coccidioides posadasii in filamentous phase (n=22) and Histoplasma capsulatum in both filamentous (n=40) and yeast phases (n=13), using the broth dilution methods as described by the Clinical and Laboratory Standards Institute, to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of these compounds. The mechanisms of action of these compounds were also investigated by analyzing their effect on cell membrane permeability and ergosterol synthesis. The MIC and MFCf these compounds against C. posadasii, mycelial H. capsulatum, and yeast-like H. capsulatum, were in the following ranges: 350-5720µg/mL, 20-2860µg/mL, and 40-1420µg/mL, respectively for terpinen-4-ol; 250-4000µg/mL, 30-2000µg/mL, and 10-1000µg/mL, respectively, for tyrosol; and 0.48-7.8µg/mL, 0.25-16µg/mL, and 0.125-4µg/mL, respectively for ß-lapachone. These compounds showed a decrease in MIC when the samples were subjected to osmotic stress, suggesting that the compounds acted on the fungal membrane. All the compounds were able to reduce the ergosterol content of the fungal strains. Finally, tyrosol was able to cause a leakage of intracellular molecules.

Synthesis and in vitro antifungal activity of isoniazid-derived hydrazones against Coccidioides posadasii.

Coccidioidomycosis is a potentially severe infection caused by dimorphic fungi Coccidioides immitis and Coccidioides posadasii. Although guidelines are well established, refractory disease is a matter of concern in the clinical management of coccidioidomycosis. In the present study three isoniazid-derived hydrazones N'-[(E)-1-(4-methoxyphenyl)ethylidene]pyridine-4-carbohydrazide, N'-[(E)-1-(4-methylphenyl)ethylidene]pyridine-4-carbohydrazide, and N'-[(E)-1-(phenyl)ethylidene]pyridine-4-carbohydrazide were synthesized and evaluated for antifungal activity against C. posadasii. Susceptibility assays were performed by macrodilution testing. Interactions between the hydrazones and amphotericin B or itraconazole were evaluated by the checkerboard method. We also investigated the impairment of such compounds on cell ergosterol and membrane integrity. The synthesized molecules were able to inhibit C. posadasii in vitro with MIC values that ranged from 25 to 400 µg/mL. Drug interactions between synthesized molecules and amphotericin B proved synergistic for the majority of tested isolates; regarding itraconazole, synergism was observed only when strains were tested against N'-[(E)-1-(phenyl)ethylidene]pyridine-4-carbohydrazide. Reduction of cellular ergosterol was observed when strains were challenged with the hydrazones alone or combined with antifungals. Only N'-[(E)-1-(4-methylphenyl)ethylidene]pyridine-4-carbohydrazide altered membrane permeability of C. posadasii cells. Isoniazid-derived hydrazones were able to inhibit C. posadasii cells causing reduction of ergosterol content and alterations in the permeability of cell membrane. This study confirms the antifungal potential of hydrazones against pathogenic fungi.

Inhibition of heat-shock protein 90 enhances the susceptibility to antifungals and reduces the virulence of Cryptococcus neoformans/Cryptococcus gattii species complex.

Heat-shock proteins (Hsps) are chaperones required for the maintenance of cellular homeostasis in different fungal pathogens, playing an important role in the infectious process. This study investigated the effect of pharmacological inhibition of Hsp90 by radicicol on the Cryptococcus neoformans/Cryptococcus gattii species complex--agents of the most common life-threatening fungal infection amongst immunocompromised patients. The influence of Hsp90 inhibition was investigated regarding in vitro susceptibility to antifungal agents of planktonic and sessile cells, ergosterol concentration, cell membrane integrity, growth at 37 °C, production of virulence factors in vitro, and experimental infection in Caenorhabditis elegans. Hsp90 inhibition inhibited the in vitro growth of planktonic cells of Cryptococcus spp. at concentrations ranging from 0.5 to 2 µg ml(-1) and increased the in vitro inhibitory effect of azoles, especially fluconazole (FLC) (P < 0.05). Inhibition of Hsp90 also increased the antifungal activity of azoles against biofilm formation and mature biofilms of Cryptococcus spp., notably for Cryptococcus gattii. Furthermore, Hsp90 inhibition compromised the permeability of the cell membrane, and reduced planktonic growth at 37 °C and the capsular size of Cryptococcus spp. In addition, Hsp90 inhibition enhanced the antifungal activity of FLC during experimental infection using Caenorhabditis elegans. Therefore, our results indicate that Hsp90 inhibition can be an important strategy in the development of new antifungal drugs.

Inhibitory activity of isoniazid and ethionamide against Cryptococcus biofilms.

In recent years, the search for drugs to treat systemic and opportunistic mycoses has attracted great interest from the scientific community. This study evaluated the in vitro inhibitory effect of the antituberculosis drugs isoniazid and ethionamide alone and combined with itraconazole and fluconazole against biofilms of Cryptococcus neoformans and Cryptococcus gattii. Antimicrobials were tested at defined concentrations after susceptibility assays with Cryptococcus planktonic cells. In addition, we investigated the synergistic interaction of antituberculosis drugs and azole derivatives against Cryptococcus planktonic cells, as well as the influence of isoniazid and ethionamide on ergosterol content and cell membrane permeability. Isoniazid and ethionamide inhibited both biofilm formation and viability of mature biofilms. Combinations formed by antituberculosis drugs and azoles proved synergic against both planktonic and sessile cells, showing an ability to reduce Cryptococcus biofilms by approximately 50%. Furthermore, isoniazid and ethionamide reduced the content of ergosterol in Cryptococcus spp. planktonic cells and destabilized or permeabilized the fungal cell membrane, leading to leakage of macromolecules. Owing to the paucity of drugs able to inhibit Cryptococcus biofilms, we believe that the results presented here might be of interest in the designing of new antifungal compounds.

Cáncer neuroendocrino de mama. A propósito de un caso / Neuroendocrine breast cancer. A case report

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Trichosporon inkin biofilms produce extracellular proteases and exhibit resistance to antifungals.

The aim of this study was to determine experimental conditions for in vitro biofilm formation of clinical isolates of Trichosporon inkin, an important opportunistic pathogen in immunocompromised patients. Biofilms were formed in microtitre plates in three different media (RPMI, Sabouraud and CLED), with inocula of 104, 105 or 106 cells ml- 1, at pH 5.5 and 7.0, and at 35 and 28 °C, under static and shaking conditions for 72 h. Growth kinetics of biofilms were evaluated at 6, 24, 48 and 72 h. Biofilm milieu analysis were assessed by counting viable cells and quantification of nucleic acids released into biofilm supernatants. Biofilms were also analysed for proteolytic activity and antifungal resistance against amphotericin B, caspofungin, fluconazole, itraconazole and voriconazole. Finally, ultrastructural characterization of biofilms formed in microtitre plates and catheter disks was performed by scanning electron microscopy. Greater biofilm formation was observed with a starter inoculum of 106 cells ml- 1, at pH 7.0 at 35 °C and 80 r.p.m., in both RPMI and Sabouraud media. Growth kinetics showed an increase in both viable cells and biomass with increasing incubation time, with maximum production at 48 h. Biofilms were able to disperse viable cells and nucleic acids into the supernatant throughout the developmental cycle. T. inkin biofilms produced more protease than planktonic cells and showed high tolerance to amphotericin B, caspofungin and azole derivatives. Mature biofilms were formed by different morphotypes, such as blastoconidia, arthroconidia and hyphae, in a strain-specific manner. The present article details the multicellular lifestyle of T. inkin and provides perspectives for further research.