Time to Start a New Enhanced Recovery After Surgery (ERAS): A Retrospective Cohort Study.

BACKGROUND: The enhanced recovery after surgery (ERAS®) is a multimodal perioperative care pathway designed to reduce surgical stress and ultimately improve patient recovery and outcome. It can require significant resources but with proven benefits. The main goal of this study was to perform a diagnostic assessment of perioperative practice in a local colorectal surgical center. METHODS: 93 patients who underwent elective colorectal surgery from January to December 2022 were analyzed. Preadmission, preoperative, and postoperative data of all patients were collected in a database developed by the researchers, according to ERAS® guidelines. Descriptive statistics were employed to summarize demographic and clinical characteristics. Chi-square and T-test were performed to identify possible associations between categorical variables and postoperative complications. RESULTS: Overall analysis showed deficient preoperative patient optimization, especially regarding nutritional counseling and supplementation, smoking and alcohol cessation, anemia treatment (9%), and pre-anesthetic medication (42%). Removal of invasive devices was significantly delayed (removal of urinary catheter average on the fourthday and surgical drain average on the fifth day) in the postoperatively period and oral intake (average onset on the sixth day). Both contribute to hospital length of stay (mean of 13 days) and a significant number of complications. CONCLUSION: The results lead us to an individual and multidisciplinary reflection on current practices and outcomes. ERAS® program, already adopted by many centers, could have a positive impact on the immediate postoperative recovery of colorectal patients in Funchal Central Hospital and implementation seems necessary.

The impact of anastomotic leakage after curative colon cancer resection on long-term survival: A retrospective cohort study / El impacto de la fuga anastomótica después de la resección curativa del cáncer de colon en la supervivencia a largo plazo: un estudio de cohorte retrospectivo

Introduction: Anastomotic leakage (AL) is one of the most feared postoperative complications in colon cancer surgery due to an association with increased morbidity and mortality, although its impact on long-term survival is not consensual. The aim of this study was to investigate the influence of AL on long-term survival of patients undergoing curative colon cancer resection. Methods: A single-centre retrospective cohort study was designed. Clinical records of all consecutive patients undergoing surgery at our institution between 01/01/2010 and 12/31/2019 were reviewed. Survival analysis was performed by Kaplan–Meier method to estimate overall and conditional survival and Cox regression to search for risk factors impacting survival. Results: A total of 2351 patients submitted to colorectal surgery were screened for eligibility, of which 686 with colon cancer were included. AL occurred in 57 patients (8,3%) and was associated with higher postoperative morbidity and mortality, length of stay and early readmissions (P < 0,05). Overall survival was inferior in the leakage group (Hazard Ratio 2,08 [1,02–4,24]). Conditional overall survival at 30, 90 days and 6 months was also inferior in the leakage group (P < 0,05), but not at 1 year. Risk factors independently associated with reduced overall survival included AL occurrence, higher ASA classification and delayed/missed adjuvant chemotherapy. AL did not impact local and distant recurrence (P > 0,05). Conclusion: AL has a negative impact on survival. Its effect is more pronounced on short-term mortality. AL does not appear to be associated with disease progression.(AU)

Objetivo: La fuga anastomótica (FA) es una complicación postoperatoria temida en la cirugía del cáncer de colon por asociación con mayor morbimortalidad, aunque su impacto en la supervivencia a largo plazo no es consensuado. Nuestro objetivo fue investigar el efecto de la FA en la supervivencia a largo plazo de pacientes sometidos a resección curativa del cáncer de colon. Métodos: Se realizó un estudio de cohorte retrospectivo unicéntrico de pacientes consecutivos intervenidos quirúrgicamente entre 01/01/2010 y el 31/12/2019. El análisis de supervivencia se realizó por el método de Kaplan-Meier para evaluar la supervivencia global (SG) y condicional y una regresión de Cox para evaluar los factores de riesgo con efecto en la supervivencia. Resultados: De 2351 pacientes sometidos a cirugía colorrectal, se incluyeron 686 con cáncer de colon. FA afectó 57 pacientes (8,3%) y se asoció con mayor morbimortalidad postoperatoria, duración de estancia hospitalaria y reingresos (P < 0,05). La SG fue inferior en el grupo de fuga (Hazard Ratio 2,08 [1,02–4,24]). La SG condicional a los 30, 90 días y 6 meses fue inferior en el grupo de fugas (P < 0,05), pero no a 1 año. Los factores de riesgo que se asociaron con SG reducida incluyeron la FA, clasificación ASA más alta y quimioterapia adyuvante retrasada/perdida. FA no afectó la recurrencia local y distante (P > 0.05). Conclusiones: FA tiene un impacto negativo en la supervivencia, con efecto más pronunciado sobre la mortalidad a corto plazo, pero no es asociado con la progresión de la enfermedad oncológica.(AU)

Design and investigation of interactions of novel peptide conjugates of purine and pyrimidine derivatives with EGFR and its mutant T790M/L858R: an in silico and laboratory study.

Peptide-based therapeutics have been gaining attention due to their ability to actively target tumor cells. Additionally, several varieties of nucleotide derivatives have been developed to reduce cell proliferation and induce apoptosis of tumor cells. In this work, we have developed novel peptide conjugates with newly designed purine analogs and pyrimidine derivatives and explored the binding interactions with the kinase domain of wild-type EGFR and its mutant EGFR [L858R/ T790M] which are known to be over-expressed in tumor cells. The peptides explored included WNWKV (derived from sea cucumber) and LARFFS, which in previous work was predicted to bind to Domain I of EGFR. Computational studies conducted to explore binding interactions include molecular docking studies, molecular dynamics simulations and MMGBSA to investigate the binding abilities and stability of the complexes. The results indicate that conjugation enhanced binding capabilities, particularly for the WNWKV conjugates. MMGBSA analysis revealed nearly twofold higher binding toward the T790M/L858R double mutant receptor. Several conjugates were shown to have strong and stable binding with both wild-type and mutant EGFR. As a proof of concept, we synthesized pyrimidine conjugates with both peptides and determined the KD values using SPR analysis. The results corroborated with the computational analyses. Additionally, cell viability and apoptosis studies with lung cancer cells expressing the wild-type and double mutant proteins revealed that the WNWKV conjugate showed greater potency than the LARFFS conjugate, while LARFFS peptide alone showed poor binding to the kinase domain. Thus, we have designed peptide conjugates that show potential for further laboratory studies for developing therapeutics for targeting the EGFR receptor and its mutant T790M/L858R.

The impact of anastomotic leakage after curative colon cancer resection on long-term survival: A retrospective cohort study.

INTRODUCTION: Anastomotic leakage (AL) is one of the most feared postoperative complications in colon cancer surgery due to an association with increased morbidity and mortality, although its impact on long-term survival is not consensual. The aim of this study was to investigate the influence of AL on long-term survival of patients undergoing curative colon cancer resection. METHODS: A single-centre retrospective cohort study was designed. Clinical records of all consecutive patients undergoing surgery at our institution between 01/01/2010 and 12/31/2019 were reviewed. Survival analysis was performed by Kaplan-Meier method to estimate overall and conditional survival and Cox regression to search for risk factors impacting survival. RESULTS: A total of 2351 patients submitted to colorectal surgery were screened for eligibility, of which 686 with colon cancer were included. AL occurred in 57 patients (8,3%) and was associated with higher postoperative morbidity and mortality, length of stay and early readmissions (P < 0,05). Overall survival was inferior in the leakage group (Hazard Ratio 2,08 [1,02-4,24]). Conditional overall survival at 30, 90 days and 6 months was also inferior in the leakage group (P < 0,05), but not at 1 year. Risk factors independently associated with reduced overall survival included AL occurrence, higher ASA classification and delayed/missed adjuvant chemotherapy. AL did not impact local and distant recurrence (P > 0,05). CONCLUSION: AL has a negative impact on survival. Its effect is more pronounced on short-term mortality. AL does not appear to be associated with disease progression.

Correction: Maternal mortality associated with COVID-19 in Brazil in 2020 and 2021: Comparison with non-pregnant women and men.

[This corrects the article DOI: 10.1371/journal.pone.0261492.].

Development of Self-Assembled Biomimetic Nanoscale Collagen-like Peptide-Based Scaffolds for Tissue Engineering: An In Silico and Laboratory Study.

Development of biocomposite scaffolds has gained tremendous attention due to their potential for tissue regeneration. However, most scaffolds often contain animal-derived collagen that may elicit an immunological response, necessitating the development of new biomaterials. Herein, we developed a new collagen-like peptide,(Pro-Ala-His)10 (PAH)10, and explored its ability to be utilized as a functional biomaterial by incorporating it with a newly synthesized peptide-based self-assembled gel. The gel was prepared by conjugating a pectin derivative, galataric acid, with a pro-angiogenic peptide (LHYQDLLQLQY) and further functionalized with a cortistatin-derived peptide, (Phe-Trp-Lys-Thr)4 (FWKT)4, and the bio-ionic liquid choline acetate. The self-assembly of (PAH)10 and its interactions with the galactarate-peptide conjugates were examined using replica exchange molecular dynamics (REMD) simulations. Results revealed the formation of a multi-layered scaffold, with enhanced stability at higher temperatures. We then synthesized the scaffold and examined its physicochemical properties and its ability to integrate with aortic smooth muscle cells. The scaffold was further utilized as a bioink for bioprinting to form three-dimensional cell-scaffold matrices. Furthermore, the formation of actin filaments and elongated cell morphology was observed. These results indicate that the (PAH)10 hybrid scaffold provides a suitable environment for cell adhesion, proliferation and growth, making it a potentially valuable biomaterial for tissue engineering.

Sputum induction and its diagnostic applications in inflammatory airway disorders: a review.

Sputum induction is a technique that covers the induction and the subsequent processing of the expectorate primarily for the analysis of cells and different inflammatory biomarkers present in the airways to further understand the pathophysiology of different inflammatory respiratory disorders such as asthma and chronic obstructive pulmonary disease (COPD) as well as the diagnosis of lung diseases such as lung cancer, tuberculosis, and Pneumocystis jirovecii pneumonia. It is a non-invasive, safe, cost-effective, and reliable technique reported to exhibit a high success rate. However, due to being technically demanding and time-consuming and having the need of employing trained staff, this technique is only used in restricted research centres and in limited centres of clinical use. When the sputum is collected after induction, the primary goal is to obtain a differential cell count and evaluate the molecular biomarkers of airway inflammation such as eosinophil cationic protein, eosinophil-derived neurotoxin, major basic protein, tryptase, cytokine production [e.g., interleukin (IL)-5], albumin, and fibrinogen. In addition, cytospins from the processed sputum are used for immunocytochemical staining of cellular products such as EG-2 reactive protein, granulocyte-macrophage colony-stimulating factor, tumour necrosis factor alpha, and IL-8 that play significant roles in understanding the pathophysiology of inflammatory airway diseases. Nowadays, this technique can be further used by performing an additional analysis such as flow cytometry and in situ hybridisation on the sputum supernatant to investigate more the immune response and pathophysiological process of such various respiratory diseases. In addition, the application of sputum fluid phase to assess the biomarkers could be used more routinely in pathological laboratories for diagnosing lung cancer, COPD, and asthma as well as for monitoring lung cancer progression and asthma and COPD treatment, allowing for early detection and a better treatment provided by the clinicians.

Serum Anti-Spike Antibodies Are Not Affected by Immunosuppressants in SARS-CoV-2 Vaccinations Given to Brazilian Patients with Inflammatory Bowel Disease.

This study aimed to evaluate humoral responses after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of patients with inflammatory bowel disease (IBD). Patients with IBD enrolled in a tertiary outpatient unit were followed up between September 2021 and September 2022 via serial blood collection. Immunoglobulin G antibody titers against SARS-CoV-2 were measured before administration and 1 and 6 months after the administration of two doses of different vaccination regimens. The results were compared with those of a healthy control group obtained during the same period. The mean pre-vaccination antibody titers were 452.0 and 93.3 AU/mL in the IBD (n = 42) and control (n = 89) groups, respectively. After two doses of the vaccine, the titers significantly increased in both groups (IBD, 8568.0 AU/mL; control, 7471.0 AU/mL; p < 0.001). One month after the second dose, no significant differences were observed between the two groups (p = 0.955). Significant differences between vaccination schemes in the IBD group were observed, with higher titers in those who received Pfizer, younger patients (p < 0.005), and those with a previous coronavirus disease 2019 (COVID-19) infection (p < 0.012). The use of immunosuppressants and immunobiologicals did not affect the overall humoral response to COVID-19 vaccine in patients with IBD, but specific vaccine regimens, age, and previous coronavirus infection significantly did. This study reinforces the positive impact of booster doses and the safety of SARS-CoV-2 vaccination.

A computational and laboratory approach for the investigation of interactions of peptide conjugated natural terpenes with EpHA2 receptor.

CONTEXT: Ephrin type A receptor 2 (EphA2) is a well-known drug target for cancer treatment due to its overexpression in numerous types of cancers. Thus, it is crucial to determine the binding interactions of this receptor with both the ligand-binding domain (LBD) and the kinase-binding domain (KBD) through a targeted approach in order to modulate its activity. In this work, natural terpenes with inherent anticancer properties were conjugated with short peptides YSAYP and SWLAY that are known to bind to the LBD of EphA2 receptor. We examined the binding interactions of six terpenes (maslinic acid, levopimaric acid, quinopimaric acid, oleanolic, polyalthic, and hydroxybetulinic acid) conjugated to the above peptides with the ligand-binding domain (LBD) of EphA2 receptor computationally. Additionally, following the "target-hopping approach," we also examined the interactions of the conjugates with the KBD. Our results indicated that most of the conjugates showed higher binding interactions with the EphA2 kinase domain compared to LBD. Furthermore, the binding affinities of the terpenes increased upon conjugating the peptides with the terpenes. In order to further investigate the specificity toward EphA2 kinase domain, we also examined the binding interactions of the terpenes conjugated to VPWXE (x = norleucine), as VPWXE has been shown to bind to other RTKs. Our results indicated that the terpenes conjugated to SWLAY in particular showed high efficacy toward binding to the KBD. We also designed conjugates where in the peptide portion and the terpenes were separated by a butyl (C4) group linker to examine if the binding interactions could be enhanced. Docking studies showed that the conjugates with linkers had enhanced binding with the LBD compared to those without linkers, though binding remained slightly higher without linkers toward the KBD. As a proof of concept, maslinate and oleanolate conjugates of each of the peptides were then tested with F98 tumor cells which are known to overexpress EphA2 receptor. Results indicated that the oleanolate-amido-SWLAY conjugates were efficacious in reducing the cell proliferation of the tumor cells and may be potentially developed and further studied for targeting tumor cells overexpressing the EphA2 receptor. To test if these conjugates could bind to the receptor and potentially function as kinase inhibitors, we conducted SPR analysis and ADP-Glo assay. Our results indicated that OA conjugate with SWLAY showed the highest inhibition. METHODS: Docking studies were carried out using AutoDock Vina, v.1.2.0; Molecular Dynamics and MMGBSA calculations were carried out through Schrodinger Software DESMOND.

High and low-fidelity simulation for respiratory diseases pediatric training: a prospective and randomized study.

OBJECTIVE: To compare high and low-fidelity simulations for the recognition of respiratory distress and failure in urgency and emergency pediatric scenarios. METHODS: 70 fourth-year medical students were randomly distributed in high and low-fidelity groups and simulated different types of respiratory problems. Theory tests, performance checklists, and satisfaction and self-confidence questionnaires were used in the assessment. Face-to-face simulation and memory retention was applied. The statistics were evaluated by averages and quartiles, Kappa, and generalized estimating equations. The p-value was considered 0.05. RESULTS: In the theory test there was an increase in scores in both methodologies (p < 0.001); in memory retention (p = 0.043) and at the end of the process the high-fidelity group had better results. The performance in the practical checklists was better after the second simulation (p > 0,05). The high-fidelity group felt more challenged in both phases (p = 0.042; p = 0.018) and showed greater self-confidence to recognize changes in clinical conditions and in memory retention (p = 0.050). The same group, in relation to the hypothetical real patient to be treated in the future, felt better confident to recognize respiratory distress and failure (p = 0.008; p = 0.004), and better prepared to make a systematic clinical evaluation of the patient in memory retention (p = 0.016). CONCLUSION: The two levels of simulations enhance diagnostic skills. High fidelity improves knowledge, leads the student to feel more challenged and more self-confident in recognizing the severity of the clinical case, including memory retention, and showed benefits regarding self-confidence in recognizing respiratory distress and failure in pediatric cases.

Interactions of Nanoscale Self-Assembled Peptide-Based Assemblies with Glioblastoma Cell Models and Spheroids.

Peptide nanoassemblies have garnered remarkable importance in the development of novel nanoscale biomaterials for drug delivery into tumor cells. Taking advantage of receptor mediated recognition of two known peptides, angiopep-2 (TFFYGGSRGKRNNFKTEEY) and A-COOP-K (ACGLSGLC10 VAK) that bind to the over-expressed receptors low density lipoprotein (LRP-1) and fatty acid binding protein (FABP3) respectively, we have developed new peptide conjugates by combining the anti-inflammatory, antitumor compound azelaic acid with angiopep-2, which efficiently self-assembled into nanofibers. Those nanofibers were then functionalized with the A-COOP-K sequence and formed supramolecular hierarchical structures that were found to entrap the chemotherapeutic drug doxorubicin efficaciously. Furthermore, the nanoassemblies were found to release the drug in a dose-dependent manner and showed a stepwise increase over a period of 2 weeks under acidic conditions. Two cell lines (U-87-MG and U-138-MG) were utilized as models for glioblastoma cells grown in the presence of serum and under serum-free conditions to mimic the growth conditions of natural tumors. The drug entrapped assemblies were found to inhibit the cell proliferation of both U-87 and U-138MG glioblastoma cells. Three dimensional spheroids of different sizes were grown to mimic the tumors and evaluate the efficacy of drug release and internalization. Our results indicated that the nanoassemblies were found to have higher internalization of DOX and were well-spread throughout the spheroids grown, particularly under serum-free conditions. The nanoassemblies also displayed blood-brain barrier penetration when tested with a multicellular in vitro model. Such self-assembled nanostructures with targeting ability may provide a suitable platform for the development of new peptide-based biomaterials that can provide more insights about the mechanistic approach for drug delivery for not only 2D cell cultures but also 3D tumoroids that mimic the tumor microenvironments.

High and low-fidelity simulation for respiratory diseases pediatric training: a prospective and randomized study

Abstract Objective: To compare high and low-fidelity simulations for the recognition of respiratory distress and failure in urgency and emergency pediatric scenarios. Methods: 70 fourth-year medical students were randomly distributed in high and low-fidelity groups and simulated different types of respiratory problems. Theory tests, performance checklists, and satisfaction and self-confidence questionnaires were used in the assessment. Face-to-face simulation and memory retention was applied. The statistics were evaluated by averages and quartiles, Kappa, and generalized estimating equations. The p-value was considered 0.05. Results: In the theory test there was an increase in scores in both methodologies (p < 0.001 ); in memory retention (p = 0.043) and at the end of the process the high-fidelity group had better results. The performance in the practical checklists was better after the second simulation (p > 0,05). The high-fidelity group felt more challenged in both phases (p = 0.042; p = 0.018) and showed greater self-confidence to recognize changes in clinical conditions and in memory retention (p = 0.050). The same group, in relation to the hypothetical real patient to be treated in the future, felt better confident to recognize respiratory distress and failure (p = 0.008; p = 0.004), and better prepared to make a systematic clinical evaluation of the patient in memory retention (p = 0.016). Conclusion: The two levels of simulations enhance diagnostic skills. High fidelity improves knowledge, leads the student to feel more challenged and more self-confident in recognizing the severity of the clinical case, including memory retention, and showed benefits regarding self-confidence in recognizing respiratory distress and failure in pediatric cases.

Teamwork in Pediatric Resuscitation: Training Medical Students on High-Fidelity Simulation.

Background: Simulation training and teamwork for medical students are essential to improve performance in pediatric cardiopulmonary resuscitation. Purpose: To evaluate if a specific approach to teamwork improves technical and nontechnical performance. Methods: We performed quasiexperimental, prospective, pre- and postinterventional, and nonrandomized research with 65 students in the fourth year of their medicine course. This was a case-control study in which teams used a customized TeamSTEPPS protocol (n=34) or not (n=31) for cardiopulmonary arrest training in children using high-fidelity simulation. All participants answered a sociodemographic and satisfaction questionnaire and underwent theory and practice pre- and posttesting. The survey data were collected in 2019 and analyzed using χ2, Mann-Whitney, κ, and Wilcoxon tests. p<0.05 was considered significant. Results: Intervention and control groups achieved better scores in theory posttesting (p<0.001 and p=0.049), but there was no difference between them in pre- (p=0.291) and posttesting (p=0.397). In the checklist of the practice test, all groups obtained their best outcomes in posttesting and the intervention group achieved higher scores (p<0.001). All groups increased the number of teamwork events and reduced the time span to perform resuscitation first steps (p<0.001) in posttesting. Conclusion: The use of teamwork training based on a customized TeamSTEPPS protocol improved performance in team behavior and group technical achievement. The evaluation of the students about the training was positive.

A Combination of Curcuma longa and Diazepam Attenuates Seizures and Subsequent Hippocampal Neurodegeneration.

Epilepsy is one of the most common neurological disorders, which occurs due to the instability in the inhibitory and excitatory synaptic transmissions in the brain. However, many patients develop resistance to the available drugs, which results in cell degeneration caused due to inadequate control of the seizures. Curcumin, Curcuma longa, is known to be effective for the treatment of organic disorders and may prevent seizures, reduce oxidative stress, and decrease brain damage. Given this, the present study evaluated the antiepileptic effects of C. longa in comparison with both the diazepam and the combined application of these two substances, in terms of their effects on the brain activity and the potential histopathological changes in the hippocampus. This study used male Wistar rats (age: 10-12 weeks; weight: 260 ± 20 g), which were pretreated for 4 days with either saline, C. longa, diazepam, or C. longa + diazepam; and on the fifth day, pentylenetetrazol (PTZ) was administered to induce the seizure. In the C. longa group, a significant increase was observed in the latency of the onset of seizure-related behavior. Surprisingly, however, the combined treatment resulted in the best control of the seizure-related behavior, with the greatest latency of the onset of spasms and isolated clonic seizures. This group also obtained the best results in the electroencephalographic trace and seizure control, with a reduction in the frequency and amplitude of the spike-waves. In the saline group, PTZ significantly reduced the number of cells present in the CA1 and CA3 regions of the hippocampus, while the combined treatment obtained the best results in terms of the preservation of the neuron-like cells. These findings indicate that C. longa may contribute to the control of both seizures and the cell damage induced by PTZ, and that its association with diazepam may be a potentially effective option for the treatment of epilepsy in the future.

FOXP3 variants are independently associated with transforming growth factor Β1 plasma levels in female patients with inflammatory bowel disease.

OBJECTIVE: The aim of this study was to evaluate the association of -924 G>A (rs2232365) and -3279 C>A (rs3761548) FOXP3 variants with IBD susceptibility, clinical and endoscopic activity, and IL-10 and TGF-ß1 plasma levels. METHOD: The study included 110 IBD female patients, 60 with Ulcerative Colitis (UC) and 50 with Crohn's Disease (CD), and 154 female controls. FOXP3 variants were determined with Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Plasma levels of IL-10 and TGF-ß1 were determined using immunofluorimetric assay. RESULTS: AA genotype of rs2232365 and rs3761548 was associated with CD (OR = 3.147, 95% CI 1.015-9.758, p = 0.047) and UC (OR = 3.221, 95% CI 1.050-9.876, p = 0.041) susceptibility, respectively. However, were not associated with TGF-ß1 and IL-10 levels, and endoscopic/clinical activity disease. GAGA haplotype was associated with IBD (OR = 4.003, 95% CI 1.100-14.56, p = 0.035) and UC susceptibility (OR = 6.107, 95% CI 1.609-23.18, p = 0.008). In addition, IBD patients with the GAGA haplotype had lower TGF-ß1 levels (p = 0.041). Moreover, G/C haplotype (dominant model) had a protective effect of 60% in CD susceptibility and lower Endoscopic Severity Index. CONCLUSIONS: These results suggest that FOXP3 variants could exert a role in the Treg, which could be one of the factors involved in the susceptibility and pathogenesis of IBD.

Figure-based speech perception test: applicability in children with Down syndrome. / Teste de percepção de fala com figuras: aplicabilidade em crianças com síndrome de Down.

PURPOSE: To verify the applicability of the picture-based speech perception test in children with Down syndrome. METHODS: Observational, descriptive, prospective study, carried out at two speech therapy centers, approved by their Research Ethics Committees under numbers 82522217.5.0000.5440 and 79510317.8.0000.5257. A total of 41 children with Down syndrome, of both sexes, aged 2 years to 10 years and 11 months participated. They were divided into three groups: GI (2 years to 4 years and 11 months); GII (5 years to 7 years and 11 months); GIII (8 years to 10 years and 11 months). We verified their medical history and carried out meatoscopy, pure-tone threshold audiometry, speech recognition threshold test with pictures, and immittance tests. For statistical analysis, we used Fisher's Exact Test with the 5% significance level. Results: The analysis of hits and misses in relation to chronological age revealed significance in seven words: "ice", "knife", "cow", "key", "mouse", "dog", and "sun". We then analyzed this study participants' performance in the speech test with pictures and those in the study that developed and validated this test. Comparing the percentage of correct answers in the two groups, we found that the words with the most correct answers were "hand", "house", and "frog". Conclusion: The test applied in this study provides a clear and objective interpretation of the results, regardless of the child's verbal production.

OBJETIVO: Verificar a aplicabilidade do teste de percepção de fala com figuras em crianças com síndrome de Down. MÉTODO: Estudo observacional, descritivo e prospectivo, realizado em dois centros fonoaudiológicos, aprovado pelos Comitês de Ética em Pesquisa sob número 82522217.5.0000.5440 e 79510317.8.0000.5257. Participaram 41 crianças com síndrome de Down, de ambos os sexos, com idade entre dois anos e dez anos e 11 meses, as quais foram divididas em três grupos: GI (dois a quatro anos e 11 meses); GII (cinco a sete anos e 11 meses) e GIII (oito a dez anos e 11 meses). Foram realizados os procedimentos de anamnese, meatoscopia, audiometria tonal liminar, teste de limiar de recepção de fala com figuras e imitanciometria. Para a análise estatística, Teste Exato de Fisher com nível de significância de 5%. RESULTADOS: Ao ser analisado o número de acertos e erros, em relação à idade cronológica, foi encontrada significância para sete palavras: gelo, faca, vaca, chave, rato, cão e sol. Foi analisado, posteriormente, o desempenho no teste de fala com figuras, dos participantes desse estudo e o desempenho dos participantes do estudo que elaborou e validou este teste. Foi observado que, quando se equiparou a porcentagem de acertos nos dois grupos, as palavras com maior ocorrência de acertos foram: mão, casa e sapo. Conclusão: O teste aplicado nesse estudo proporciona a interpretação do resultado de forma clara e objetiva e independe da produção verbal da criança.

Chagas disease is an independent predictor of stroke and death in a cohort of heart failure patients.

BACKGROUND AND AIMS: Chagas disease is a common cause of heart failure (HF) and death in developing countries. Although stroke is known to occur in these patients, an accurate estimate of stroke incidence is lacking. We aimed to determine the incidence of stroke and death in patients with HF, comparing Chagas and non-Chagas etiologies. METHODS: Cohort of stroke-free patients with HF (Framingham criteria) followed in a university-based outpatient clinic in Brazil. Baseline characteristics included sociodemographic, risk factor assessment, echocardiographic and electrocardiographic findings. Chagas disease was defined by appropriate serologic tests. Cause-specific Cox regression was used to search for predictors of stroke or death as separate outcomes. RESULTS: We studied 565 patients with HF between January 2003 and December 2018, mean age 54.3 ± 12.9 years, 305 (54.0%) females, 271/535 (50.7%) with Chagas disease. Chagas patients were older (55.5 vs. 53.1 years), more frequently women (60.5% vs. 47.3%), less frequently harbored coronary artery disease (14.5% vs. 34.1%) when compared to non-Chagas patients. Echocardiography showed more severe disease among non-Chagas patients [median left ventricle ejection fraction (LVEF) 37.3% vs. 47.0%]. Over a mean 42.9 (±34.4) months, we followed 404 (71.5%) patients, completing 1442 patient-years of follow-up. Stroke incidence was higher in Chagas when compared to non-Chagas patients (20.2 vs. 13.9 events per 1000 patient-years), while death rate was similar (41.6 vs. 43.1 deaths per 1000 patient-years). In the multivariable analysis for stroke outcome adjusted for LVEF and arrhythmias, cause-specific hazard ratio (CSHR) for Chagas was 2.54 (95% confidence interval 1.01-6.42, p = 0.048). Chagas disease was also associated with increased risk of death (CSHR 1.83; 95% confidence interval 1.04-3.24, p = 0.037). CONCLUSION: Chagas disease is associated with increased risk of stroke and death when compared to other etiologies of HF, independently of HF severity or cardiac arrhythmias, suggesting other factors contribute to increased stroke risk and mortality in Chagas disease. Early prevention and treatment of Chagas disease is imperative to reduce a later risk of stroke in endemic areas.

COVID-19: quais motivos levaram os pacientes a procurarem pronto atendimento oftalmológico durante a pandemia? / COVID-19: what reasons led patients to seek emergency care during the pandemic?

RESUMO Objetivo Analisar o motivo pelo qual pacientes procuraram o pronto atendimento oftalmológico durante a pandemia da COVID-19. Métodos Estudo de corte transversal, retrospectivo, realizado a partir da análise de prontuários de pacientes atendidos em um pronto atendimento oftalmológico de um serviço privado da cidade de Santos (SP) entre 11 de março de 2020 e 16 de julho de 2020. Resultados Foram atendidos 386 pacientes no período analisado. A maior parte das consultas (60,36%) deu-se a pessoas do sexo feminino. Pessoas da faixa etária entre 19 e 59 anos foram as que mais procuraram o pronto atendimento (57,25%). Ao se considerar a profissão desses pacientes, estudantes e aposentados apresentaram a mesma proporção (10,26%) seguidos de pessoas do lar (6,99%). Do total de casos atendidos, 59 pacientes foram diagnosticados com conjuntivite, enquanto 58 tiveram diagnóstico de traumatismo de olho e órbita. Conclusão No período analisado, o pronto atendimento oftalmológico recebeu, predominantemente, mulheres na faixa etária entre 19 e 59 anos, e os diagnósticos mais frequentes foram de conjuntivite e trauma.

ABSTRACT Objective To analyze the reason why patients sought emergency eye care during the pandemic of COVID-19. Methods This was a retrospective cross-sectional study based on the analysis of medical records of patients seen at an ophthalmology emergency department of a private service in the city of Santos (SP) between March 11, 2020 and July 16, 2020. Results A total of 386 patients were seen in the analyzed period. Most appointments (60.36%) were attended by women. People between 19 and 59 years old were the ones who most sought the emergency room (57.25%). When considering the profession of these patients, students and retired people presented the same proportion (10.26%), followed by housewives (6.99%). Of the total number of cases seen, 59 patients were diagnosed with conjunctivitis, while 58 were diagnosed with eye and orbit trauma. Conclusion In the analyzed period, the ophthalmology emergency care predominantly received women in the age group between 19 and 59 years old, and the most frequent diagnoses were conjunctivitis and trauma.

FOXP3 variants are independently associated with transforming growth factor B1 plasma levels in female patients with inflammatory bowel disease

Abstract Objective: The aim of this study was to evaluate the association of -924 G>A (rs2232365) and -3279 C>A (rs3761548) FOXP3 variants with IBD susceptibility, clinical and endoscopic activity, and IL-10 and TGF-β1 plasma levels. Method: The study included 110 IBD female patients, 60 with Ulcerative Colitis (UC) and 50 with Crohn's Disease (CD), and 154 female controls. FOXP3 variants were determined with Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Plasma levels of IL-10 and TGF-β1 were determined using immuno-fluorimetric assay. Results: AA genotype of rs2232365 and rs3761548 was associated with CD (OR = 3.147, 95% CI 1.015-9.758, p = 0.047) and UC (OR = 3.221, 95% CI 1.050-9.876, p = 0.041) susceptibility, respectively. However, were not associated with TGF-β1 and IL-10 levels, and endoscopic/clinical activity disease. GAGA haplotype was associated with IBD (OR = 4.003, 95% CI 1.100-14.56, p = 0.035) and UC susceptibility (OR = 6.107, 95% CI 1.609-23.18, p = 0.008). In addition, IBD patients with the GAGA haplotype had lower TGF-β1 levels (p = 0.041). Moreover, G/C haplotype (dominant model) had a protective effect of 60% in CD susceptibility and lower Endoscopic Severity Index. Conclusions: These results suggest that FOXP3 variants could exert a role in the Treg, which could be one of the factors involved in the susceptibility and pathogenesis of IBD.