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BACKGROUND: Anthracycline-based chemotherapy represents a cornerstone treatment for a number of common cancers, including breast cancer, lymphoma, and sarcoma. However, anthracycline-induced cardiotoxicity remains a significant concern, often presenting as a decline in cardiac function which can ultimately lead to heart failure (HF) or asymptomatic left ventricular dysfunction, in up to 10-15% of patients.Sodium-glucose transport protein 2 inhibitor (SGLT2i) therapies have been demonstrated to reduce the incidence of HF in high-risk non-cancer patients. Preliminary retrospective data suggest their role in mitigating the incidence of HF during or after anthracycline treatment METHODS: The EMPACARD-PILOT trial was a prospective caseâcontrol study involving breast cancer patients scheduled to undergo anthracycline-based chemotherapy in a 4-cycle protocol of 60 mg/m2 doxorubicin. We used the HFA/ICOS risk score to identify patients at high or very high risk of cardiotoxicity. Patients with diabetes mellitus or stable heart failure with preserved ejection fraction (HFpEF) were prescribed empagliflozin (10 mg per day), starting seven days before the administration of anthracyclines and continuing for a period of six months. Those not meeting these criteria served as controls. The primary endpoint was cancer therapy-related cardiac dysfunction (CTRCD) incidence. CTRCD was defined as either a decrease in left ventricular ejection fraction (LVEF) of at least 10% to a final value below 50% or a reduction in global longitudinal strain (GLS) of at least 15% from baseline at any point during the study. The secondary endpoints included mortality and hospitalization due to cardiovascular causes or clinical heart failure. Exploratory endpoints included increases in serum troponin and NT-proBNP levels and a decrease in the glomerular filtration rate (GFR). The safety endpoints tracked includedketoacidosis, hypoglycemia, sepsis, neutropenic fever, and urinary tract infections. RESULTS: During the enrollment period, 785 breast cancer patients were analysed. Of these, 107 met the inclusion criteria, and 76 subsequently provided informed consent. The study was conducted with comparable adherence rates of 81.5% in both the empagliflozin group (n = 38) and the control group (n = 38). The follow-up data from 62 patients revealed a significant reduction in the primary outcome within 6 months for the empagliflozin group compared with the control group (6.5% vs. 35.5%, p = 0.005), with a relative risk of 0.18 (95% CI: 0.04-0.75). Compared with the control treatment, treatment with empagliflozin also significantly preserved the ejection fraction at 6 months follow-up (56.8% ± 5.8% vs. 53.7% ± 6.7, p = 0.029). However, there were no significant differences between the groups in terms of NT-proBNP, cTnI, clinical heart failure, GFR, or mortality/hospitalization due to heart failure. CONCLUSION: Empagliflozin is associated with reduced incidence of CTRCD in high-risk patients treated with anthracyclines. These data should serve as the foundation for a clinical trial to test whether SGLT2 inhibitors can reduce the incidence of heart failure in this patient group.
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Considering a circular economy perspective, this study evaluates the possible effect of targeted short-term supplementation with Withania somnifera L. (WS; Ashwagandha) on ram's seminal quality, socio-sexual behaviors, and blood constituents. Black Belly rams (n = 20) received a basal diet comprising feed-leftovers from dairy cows in the north-arid Mexico (i.e., Comarca Lagunera CL). The experimental units, with proven libido and fertility, were homogeneous in terms of age (3.41 ± 0.21 yr.), live weight (LW; 53.8 ± 3.3 kg), body condition (BC; 2.96 ± 0.01 units), initial sperm concentration (2387 ± 804 × 106), and viability (23.9 ± 15.6%). Rams were randomly assigned during the transition reproductive period (i.e., May to Jun; 25° NL) to three treatment groups: non-supplemented control group (CONT; n = 6), low WS-supplemented (LWS; i.e., 100 mg kg LW-1 d-1 × 40 d; n = 7), and high-WS-supplemented (HWS; i.e., 200 mg kg LW-1 d-1 × 40 d; n = 7). The basal leftover diet was offered twice daily (0700 and 1600 h); the experimental period (EP) lasted 47 d. No differences (p > 0.05) among treatments occurred regarding LW and BCS at the onset of the EP. Whereas the greater scrotal circumference (SCRC, cm) arose in the LWS and CONT rams, an increased ejaculated volume (VOLEJA, mL) occurred in the WS-rams. A total of 5/9 (i.e., 55%) appetitive and 3/3 (i.e., 100%) consummatory sexual behaviors favored (p < 0.05) the WS-rams, particularly the HWS rams, towards the final EP. The same was true (p < 0.05) regarding the hemogram variables white blood cell count (×109 cells L-1), hemoglobin concentration (g dL-1), and medium corpuscular volume (fL). This study, based on a rethink-reuse-reduce enquiry approach, enabled connectedness between two noteworthy animal systems in the CL: dairy cows and meat sheep schemes. Certainly, the use of dairy cow feed-leftovers aligned with the short-term supplementation with WS promoted enhanced testicular function, augmented seminal volume, and an increased sexual behavior in Black Belly rams in northern Mexico. Finally, while our research outcomes should enhance not only the resilience and sustainability of sheep production and the well-being of sheep-producers and their families, it may also embrace clinical translational applications.
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PURPOSE: We developed a predictive model to assess the risk of major bleeding (MB) within 6 months of primary venous thromboembolism (VTE) in cancer patients receiving anticoagulant treatment. We also sought to describe the prevalence and incidence of VTE in cancer patients, and to describe clinical characteristics at baseline and bleeding events during follow-up in patients receiving anticoagulants. METHODS: This observational, retrospective, and multicenter study used natural language processing and machine learning (ML), to analyze unstructured clinical data from electronic health records from nine Spanish hospitals between 2014 and 2018. All adult cancer patients with VTE receiving anticoagulants were included. Both clinically- and ML-driven feature selection was performed to identify MB predictors. Logistic regression (LR), decision tree (DT), and random forest (RF) algorithms were used to train predictive models, which were validated in a hold-out dataset and compared to the previously developed CAT-BLEED score. RESULTS: Of the 2,893,108 cancer patients screened, in-hospital VTE prevalence was 5.8% and the annual incidence ranged from 2.7 to 3.9%. We identified 21,227 patients with active cancer and VTE receiving anticoagulants (53.9% men, median age of 70 years). MB events after VTE diagnosis occurred in 10.9% of patients within the first six months. MB predictors included: hemoglobin, metastasis, age, platelets, leukocytes, and serum creatinine. The LR, DT, and RF models had AUC-ROC (95% confidence interval) values of 0.60 (0.55, 0.65), 0.60 (0.55, 0.65), and 0.61 (0.56, 0.66), respectively. These models outperformed the CAT-BLEED score with values of 0.53 (0.48, 0.59). CONCLUSIONS: Our study shows encouraging results in identifying anticoagulated patients with cancer-associated VTE who are at high risk of MB.
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PURPOSE: Both venous and arterial thrombotic events (VTE/AT) can be associated with Immune Checkpoint Inhibitors (ICI). However, there is a paucity of information apropos patients in routine clinical practice. METHODS: /Patients. This retrospective, multicenter study was promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Individuals with head and neck cancer who initiated ICI between 01/01/2015 and 31/12/2021 were recruited. Minimum follow-up was 6 months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT, with secondary objectives including the analysis of their impact on survival and the identification of variables predictive of VTE/AT. RESULTS: A total of 143 patients with head and neck cancer were enrolled. The incidence of VTE/AT during follow-up (median 8.6 months) was 2.8%. Survival analysis showed no significant differences (p = 0.644) between the group that developed VTE/AT (median 7.13 months, 95% CI 0-22.9) and the group that did not (median 9.86 months, 95% CI 6.3-13.4). The presence of liver metastases was predictive of VTE/AT (p < 0.05). CONCLUSIONS: Thromboembolic disease associated with immunotherapy in patients with head and neck neoplasia does not significantly impact survival. The presence of liver metastases can predict these events.
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Plant breeding [...].
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Variação Genética , Plantas , Estresse Fisiológico , Estresse Fisiológico/genética , Plantas/genética , Melhoramento Vegetal/métodos , Fenômenos Fisiológicos Vegetais , Adaptação Fisiológica/genéticaRESUMO
The human microbiome has a crucial role in the homeostasis and health of the host. These microorganisms along with their genes are involved in various processes, among these are neurological signaling, the maturation of the immune system, and the inhibition of opportunistic pathogens. In this sense, it has been shown that a healthy ocular microbiota acts as a barrier against the entry of pathogens, contributing to the prevention of infections. In recent years, a relationship has been suggested between microbiota dysbiosis and the development of neurodegenerative diseases. In patients with glaucoma, it has been observed that the microbiota of the ocular surface, intraocular cavity, oral cavity, stomach, and gut differ from those observed in healthy patients, which may suggest a role in pathology development, although the evidence remains limited. The mechanisms involved in the relationship of the human microbiome and this neurodegenerative disease remain largely unknown. For this reason, the present review aims to show a broad overview of the influence of the structure and composition of the human oral and gut microbiota and relate its dysbiosis to neurodegenerative diseases, especially glaucoma.
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Disbiose , Glaucoma , Microbiota , Humanos , Glaucoma/microbiologia , Microbiota/fisiologia , Disbiose/complicações , Disbiose/imunologia , Boca/microbiologia , Microbioma Gastrointestinal/fisiologia , Olho/microbiologia , Doenças Neurodegenerativas/microbiologiaRESUMO
BACKGROUND: Limited data exist on the prognostic significance of the chronology of VTE in patients with PDAC. METHODS: Medical data and survival characteristics of patients treated for PDAC from 2019 to 2021 were retrospectively reviewed. Early VTE was defined as occurring within the three months of PDAC diagnosis. RESULTS: 197 patients were included, 54 (27.4%) developed a VTE. Early appearance of VTE was associated with worse prognosis: median overall survival (mOS) VTE < 3 months 8.5 months (HR 1.65, 95% CI 1.11-2.46; p = 0.014), mOS VTE > 3 months 12.8 months (HR 0.78, 95% CI 0.39-1.54; p = 0.5) and mOS patients without VTE 11.4 months (95% CI 10.1-15.4). There was no significant association between the patient's VTE risk according to the Khorana risk score (KRS) (chi2 test p-value = 0.9). CONCLUSION: Early VTE is a prognostic factor in PDAC, which may identify a more aggressive subtype.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/mortalidade , Feminino , Masculino , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/complicações , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Prognóstico , Fatores de Tempo , Taxa de Sobrevida , Fatores de Risco , Idoso de 80 Anos ou maisRESUMO
Regenerative medicine (RM) has emerged as a promising and revolutionary solution to address a range of unmet needs in healthcare, including ophthalmology. Moreover, RM takes advantage of the body's innate ability to repair and replace pathologically affected tissues. On the other hand, despite its immense promise, RM faces challenges such as ethical concerns, host-related immune responses, and the need for additional scientific validation, among others. The primary aim of this review is to present a high-level overview of current strategies in the domain of RM (cell therapy, exosomes, scaffolds, in vivo reprogramming, organoids, and interspecies chimerism), centering around the field of ophthalmology. A search conducted on clinicaltrials.gov unveiled a total of at least 209 interventional trials related to RM within the ophthalmological field. Among these trials, there were numerous early-phase studies, including phase I, I/II, II, II/III, and III trials. Many of these studies demonstrate potential in addressing previously challenging and degenerative eye conditions, spanning from posterior segment pathologies like Age-related Macular Degeneration and Retinitis Pigmentosa to anterior structure diseases such as Dry Eye Disease and Limbal Stem Cell Deficiency. Notably, these therapeutic approaches offer tailored solutions specific to the underlying causes of each pathology, thus allowing for the hopeful possibility of bringing forth a treatment for ocular diseases that previously seemed incurable and significantly enhancing patients' quality of life. As advancements in research and technology continue to unfold, future objectives should focus on ensuring the safety and prolonged viability of transplanted cells, devising efficient delivery techniques, etc.
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Oftalmologia , Humanos , Medicina Regenerativa , Qualidade de Vida , Olho , Terapia Baseada em Transplante de Células e TecidosRESUMO
PURPOSE: The CoVID-TE model was developed with the aim of predicting venous thrombotic events (VTE) in cancer patients with Sars-Cov-2 infection. Moreover, it was capable of predicting hemorrhage and mortality 30 days following infection diagnosis. The model is pending validation. METHODS/PATIENTS: Multicenter retrospective study (10 centers). Adult patients with active oncologic disease/ antineoplastic therapy with Sars-Cov-2 infection hospitalized between March 1, 2020 and March 1. 2022 were recruited. The primary endpoint was to study the association between the risk categories of the CoVID-TE model and the occurrence of thrombosis using the Chi-Square test. Secondary endpoints were to demonstrate the association between these categories and the occurrence of post-diagnostic Sars-Cov-2 bleeding/ death events. The Kaplan-Meier method was also used to compare mortality by stratification. RESULTS: 263 patients were enrolled. 59.3% were men with a median age of 67 years. 73.8% had stage IV disease and lung cancer was the most prevalent tumor (24%). A total of 86.7% had an ECOG 0-2 and 77.9% were receiving active antineoplastic therapy. After a median follow-up of 6.83 months, the incidence of VTE, bleeding, and death 90 days after Sars-Cov-2 diagnosis in the low-risk group was 3.9% (95% CI 1.9-7.9), 4.5% (95% CI 2.3-8.6), and 52.5% (95% CI 45.2-59.7), respectively. For the high-risk group it was 6% (95% CI 2.6-13.2), 9.6% (95% CI 5.0-17.9), and 58.0% (95% CI 45.3-66.1). The Chi-square test for trends detected no statistically significant association between these variables (p > 0.05). Median survival in the low-risk group was 10.15 months (95% CI 3.84-16.46), while in the high-risk group it was 3.68 months (95% CI 0.0-7.79). The differences detected were not statistically significant (p = 0.375). CONCLUSIONS: The data from our series does not validate of the CoVID-TE as a model to predict thrombosis, hemorrhage, or mortality in cancer patients with Sars-Cov-2 infection.
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Antineoplásicos , COVID-19 , Neoplasias , Trombose , Tromboembolia Venosa , Adulto , Masculino , Humanos , Idoso , Feminino , COVID-19/complicações , SARS-CoV-2 , Estudos Retrospectivos , Teste para COVID-19 , Hemorragia , Trombose/etiologia , Neoplasias/complicaçõesRESUMO
Essential habitats support specific functions for species, such as reproduction, feeding or refuge. For highly mobile aquatic species, identifying essential habitats within the wider distribution range is central to understanding species ecology, and underpinning effective management plans. This study examined the movement and space use patterns of sevengill sharks (Notorynchus cepedianus) in Caleta Valdés (CV), a unique coastal habitat in northern Patagonia, Argentina. Seasonal residency patterns of sharks were evident, with higher detectability in late spring and early summer and lower during autumn and winter. The overlap between the residency patterns of sharks and their prey, elephant seals, suggests that CV functions as a seasonal feeding aggregation site for N. cepedianus. The study also found sexual differences in movement behaviour, with males performing abrupt departures from CV and showing increased roaming with the presence of more sharks, and maximum detection probability at high tide. These movements could be related to different feeding strategies between sexes or mate-searching behaviour, suggesting that CV may also be essential for reproduction. Overall, this study highlights the importance of coastal sites as essential habitats for N. cepedianus and deepens our understanding of the ecological role of this apex predator in marine ecosystems.
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Understanding the spatial and temporal frameworks of species diversification is fundamental in evolutionary biology. Assessing the geographic origin and dispersal history of highly diverse lineages of rapid diversification can be hindered by the lack of appropriately sampled, resolved, and strongly supported phylogenetic contexts. The use of currently available cost-efficient sequencing strategies allows for the generation of a substantial amount of sequence data for dense taxonomic samplings, which together with well-curated geographic information and biogeographic models allow us to formally test the mode and tempo of dispersal events occurring in quick succession. Here, we assess the spatial and temporal frameworks for the origin and dispersal history of the expanded clade K, a highly diverse Tillandsia subgenus Tillandsia (Bromeliaceae, Poales) lineage hypothesized to have undergone a rapid radiation across the Neotropics. We assembled full plastomes from Hyb-Seq data for a dense taxon sampling of the expanded clade K plus a careful selection of outgroup species and used them to estimate a time- calibrated phylogenetic framework. This dated phylogenetic hypothesis was then used to perform biogeographic model tests and ancestral area reconstructions based on a comprehensive compilation of geographic information. The expanded clade K colonized North and Central America, specifically the Mexican transition zone and the Mesoamerican dominion, by long-distance dispersal from South America at least 4.86 Mya, when most of the Mexican highlands were already formed. Several dispersal events occurred subsequently northward to the southern Nearctic region, eastward to the Caribbean, and southward to the Pacific dominion during the last 2.8 Mya, a period characterized by pronounced climate fluctuations, derived from glacial-interglacial climate oscillations, and substantial volcanic activity, mainly in the Trans-Mexican Volcanic Belt. Our taxon sampling design allowed us to calibrate for the first time several nodes, not only within the expanded clade K focal group but also in other Tillandsioideae lineages. We expect that this dated phylogenetic framework will facilitate future macroevolutionary studies and provide reference age estimates to perform secondary calibrations for other Tillandsioideae lineages.
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Human-driven plant selection, a practice as ancient as agriculture itself, has laid the foundations of plant breeding and contemporary farming [...].
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Melhoramento Vegetal , Plantas , Humanos , Plantas/genética , Agricultura , Biologia MolecularRESUMO
OBJECTIVE: To compare disease severity and mortality differences between female and male patients with congenital diaphragmatic hernia (CDH). STUDY DESIGN: We queried the CDH Study Group (CDHSG) database for CDH neonates managed between 2007 and 2018. Female and males were compared in statistical analyses using t tests, χ² tests, and Cox regression, as appropriate (P ≤ .05). RESULTS: There were 7288 CDH patients, of which 3048 (41.8%) were female. Females weighed less on average at birth than males (2.84 kg vs 2.97 kg, P < .001) despite comparable gestational age. Females had similar rates of extracorporeal life support (ECLS) utilization (27.8% vs 27.3%, P = .65). Although both cohorts had equivalent defect size and rates of patch repair, female patients had increased rates of intrathoracic liver herniation (49.2% vs 45.9%, P = .01) and pulmonary hypertension (PH) (86.6% vs 81.1%, P < .001). Females had lower survival rates at 30-days (77.3% vs 80.1%, P = .003) and overall lower survival to discharge (70.2% vs 74.2%, P < .001). Subgroup analysis revealed that increased mortality was significant among those who underwent repair but were never supported on ECLS (P = .005). On Cox regression analysis, female sex was independently associated with mortality (adjusted hazard ratio 1.32, P = .02). CONCLUSION: After controlling for the established prenatal and postnatal predictors of mortality, female sex remains independently associated with a higher risk of mortality in CDH. Further study into the underlying causes for sex-specific disparities in CDH outcomes is warranted.
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Hérnias Diafragmáticas Congênitas , Hipertensão Pulmonar , Recém-Nascido , Gravidez , Humanos , Masculino , Feminino , Resultado do Tratamento , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Estudos RetrospectivosRESUMO
INTRODUCTION: Intracranial aneurysms (IA) are a focal dilatation of the vessel wall, the rupture of these, causes subarachnoid hemorrhage. Until now, endovascular management is the ideal treatment, providing the interventionist a range of options among which the stent and coils embolization stands out because of its occlusion rate. This study presents the results of a retrospective cohort comparing the effectiveness, morbidity, and mortality of IA treatment with laser-cut stent-assisted coils versus braided stents. METHODOLOGY: Retrospective cohort of patients diagnosed with unruptured intracranial aneurysms treated with coil-assisted laser-cut stents or braided stents between January 2014 and December 2021. RESULTS: In total, 138 patients with 147 intracranial aneurysms were analyzed, 91 of them were treated with laser-cut stent and 56 with braided stents. The main antecedent was arterial hypertension (48.55%). In the immediate angiographic control, a Raymond Roy scale (RRO) I was obtained in 86.81% of the patients with laser-cut stents and 87.50% of the patients with braided stents. In the angiographic follow-up at 12 months, an RRO I occlusion rate of 85.19% was reported in both groups. Perioperative complications occur in 16 patients treated with laser-cut stents and 12 patients treated with braided stents. Three patients presented bleeding complications during the 12-month follow-up, of which two correspond to patients treated with braided stents and one with a laser-cut stent. CONCLUSION: Treatment of patients with intracranial aneurysms with laser-cut stents or braided stents and coils is just as safe and effective.
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In recent years, domestic laundry has been recognized as a relevant source of microfiber (MF) pollution to aquatic environments. Nevertheless, the MF emissions from industrial washing processes in real world scenarios have not been quantified. The aim of this study was to quantify the MF emissions from 3 industrial washing processes (rinse wash, acid wash and enzymatic wash) commonly employed in the manufacturing process of blue jeans. The blue jeans were characterized by ATR-FT-IR, SEM and TGA to study the morphology, the polymer chemical identity and the proportion of synthetic and natural fibers, respectively. The MF emissions were quantified as the MF mass and number emitted per washed jean. All the industrial washing processes released a majority of synthetic MF. The enzymatic wash produced the highest amount of MF, with 1423 MF per gram of fabric (MF/g) equivalent to 381.7 MF grams per gram of fabric (MF g/g), followed by the acid wash with 253 MF/g equivalent to 142.7 MF g/g and lastly the rinse wash with 133 MF/g equivalent to 62.3 MF g/g. Statistically significant differences between the MF sizes for all washing processes were found when evaluating the emissions by MF/g, however, the previous trend was not found for MF g/g. Moreover, the total MF emissions of an industrial washing process of a pair of blue jeans during its manufacture process are up to 10.95 times higher than the reported domestic washing estimates performed by the consumer available in the published literature. We demonstrate that studying industrial washing procedures of textile garments will improve the accuracy of the current estimates of MF emissions available in published reports, which will ultimately aid in the development of regulations for MF emissions at an industrial level.
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Lavanderia , Plásticos , Microplásticos , Espectroscopia de Infravermelho com Transformada de Fourier , Lavanderia/métodos , TêxteisRESUMO
The relief of the impediment to urinary flow is the treatment of acute kidney failure due to urinary tract obstruction. However, there is a risk of inducing massive polyuria, which can be self-limited or produce severe contraction of the intravascular volume with pre-renal acute kidney failure and alterations in the internal environment. Polyuria, urine output > 3 L/d or > 200 mL/min for more than 2 hours, can have multiple causes, and can be classified as osmotic, aqueous or mixed. Post-obstructive polyuria obeys different pathogenic mechanisms, which overlap and vary during a patient's evolution. Initially, there is a decrease in vasoconstrictor factors and an increase in renal blood flow, which, added to the excess of urea accumulated, will cause intense osmotic diuresis (osmotic polyuria due to urea). Added to these factors are the positive sodium and water balance during acute renal failure, plus the contributions of crystalloid solutions to replace diuresis (ionic osmotic polyuria). Finally, there may be tubular dysfunction and decreased solutes in the renal medullary interstitium, adding resistance to the action of vasopressin. The latter causes a loss of free water (mixed polyuria). We present the case of a patient with post-obstructive polyuria where, by analyzing the clinical symptoms and laboratory alterations, it was possible to interpret the mechanisms of polyuria and administer appropriate treatment for the pathogenic mechanism.
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Humanos , Masculino , Pessoa de Meia-Idade , Poliúria/etiologia , Poliúria/fisiopatologia , Obstrução Ureteral/complicações , Obstrução Ureteral/fisiopatologia , Obstrução Uretral/fisiopatologiaRESUMO
In recent years, better knowledge of the pathophysiology of inflammatory bowel diseases (IBD) has led to a relevant expansion of the therapeutic arsenal for these conditions. Janus kinase (JAK) inhibitors are a family of small molecules that block one or more of the intracellular tyrosine kinases, including JAK-1, JAK-2, JAK-3 and TYK-2. Tofacitinib, a non-selective small molecule JAK inhibitor, and upadacitinib and filgotinib, which are selective JAK-1 inhibitors, have been approved by the US Food and Drug Administration (FDA) for moderate-to-severe active ulcerative colitis. Compared to biological drugs, JAK inhibitors have a short half-life, rapid onset of action, and no immunogenicity. Both clinical trials and real-world evidence support the use of JAK inhibitors in the treatment of IBD. However, these therapies have been linked with multiple adverse events (AEs) including infection, hypercholesterolemia, venous thromboembolism, major adverse cardiovascular events, and malignancy. While early studies recognized several potential AEs, post-marketing trials have shown that tofacitinib may increase the risk of thromboembolic diseases and major cardiovascular events. The latter are seen in patients aged 50 years or older with cardiovascular risk factors. Hence, the benefits of treatment and risk stratification need to be considered when positioning tofacitinib. Novel JAK inhibitors with a more selective effect on JAK-1 have proven to be effective in both Crohn's disease and ulcerative colitis, offering a potentially safer and efficacious therapeutic option to patients, including those with previous non-response to other therapies such as biologics. Nevertheless, long-term effectiveness and safety data are required.
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Doenças Cardiovasculares , Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Inibidores de Janus Quinases , Humanos , Inibidores de Janus Quinases/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , Janus QuinasesRESUMO
One of the current challenges is to add value to agro-industrial wastes, and the cocoa industry generates about 10 tons of cocoa pod husks in Colombia for each ton of cocoa beans, which are incinerated and cause environmental damage. This study characterized the Colombian cocoa pod husk (CPH) and to isolate and characterize cellulose microfibers (tCPH) extracted via chemical treatment and pressure. Chemical and physical analyses of CPH were performed, and a pretreatment method for CPH fibers was developed, which is followed by a hydrolysis method involving high pressure in an autoclave machine with an alkaline medium (6% NaOH), and finally, bleaching of the fiber to obtain tCPH. The tCPH cellulose microfibers were also chemically and physically analyzed and characterized by infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and thermo-gravimetric analysis (TGA). Chemical and physical characterization showed a decrease in lignin content in tCPH. FTIR analysis showed the absence of some peaks in tCPH with respect to the CPH spectrum; XRD results showed an increase in crystallinity for tCPH compared to CPH, due to a higher presence of crystalline cellulose in tCPH. SEM images included a control fiber treated without high pressure (tCPHnpe), and agglomerated fibers were observed, whereas cellulose microfibers with a mean diameter of 10 ± 2.742 µm were observed in tCPH. Finally, with TGA and DTGA it was confirmed that in tCPH, the hemicellulose and lignin were removed more successfully than in the control fiber (tCPHnpe), showing that the treatment with pressure was effective at isolating the cellulose microfibers from cocoa pod husk.
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To achieve WHO's goal of eliminating hepatitis C virus (HCV), innovative strategies must be designed to diagnose and treat more patients. Therefore, we aimed to describe an implementation strategy to identify patients with HCV who were lost to follow-up (LTFU) and offer them re-linkage to HCV care. We conducted an implementation study utilizing a strategy to contact patients with HCV who were not under regular follow-up in 13 countries from Latin America. Patients with HCV were identified by the international classification of diseases (ICD-9/10) or equivalent. Medical records were then reviewed to confirm the diagnosis of chronic HCV infection defined by anti-HCV+ and detectable HCV-RNA. Identified patients who were not under follow-up by a liver specialist were contacted by telephone or email, and offered a medical reevaluation. A total of 10,364 patients were classified to have HCV. After reviewing their medical charts, 1349 (13%) had undetectable HCV-RNA or were wrongly coded. Overall, 9015 (86.9%) individuals were identified with chronic HCV infection. A total of 5096 (56.5%) patients were under routine HCV care and 3919 (43.5%) had been LTFU. We were able to contact 1617 (41.3%) of the 3919 patients who were LTFU at the primary medical institution, of which 427 (26.4%) were cured at a different institutions or were dead. Of the remaining patients, 906 (76.1%) were candidates for retrieval. In our cohort, about one out of four patients with chronic HCV who were LTFU were candidates to receive treatment. This strategy has the potential to be effective, accessible and significantly impacts on the HCV care cascade.