Use of nitrous oxide in the treatment of major depressive disorder and treatment-resistant major depressive disorder: A systematic review and meta-analysis nitrous oxide in depressive disorders.

Major Depressive Disorder (MDD) has, as a conventional treatment, pharmacological therapy with selective monoamine reuptake inhibitors. However, the medication does not always have a rapid action for exacerbated cases, and moreover, it is estimated that 15 to 30% of patients do not respond effectively to conventional treatment, leading to 'treatment-resistant depressive mood disorder' (TRD). Thus, it is necessary to search for new therapeutic methods for exacerbated and resistant cases. The objective of the study was to evaluate the therapeutic effects of nitrous oxide (N2O) in patients with MDD and TRD. The study was characterized as a systematic review of randomized clinical trials. Search strategy was developed using the keywords "nitrous oxide," "treatment-resistant depression," "Depression disorder," and their synonyms, searched in the databases MEDLINE, EMBASE, LILACS, and American Psychological Association. Four articles were included in the systematic review, with two of them being utilized for the meta-analysis, which comprised a total of 23 patients with MDD and 86 with TRD. A standardized mean difference (SMD) for the HDRS score at 24 h of -2.36 was found, with a 95% confidence interval (CI) of -3.37 to -1.34 (p < 0.0001; I2 = 46%). For the evaluation of the score after one week, an SMD of -0.60, 95% CI of -1.13 to -0.07 (p = 0.03; I2 = 0%) was found. In conclusion, N2O has a rapid action for managing decompensated patients, with a potential therapeutic effect for TRD. However, more studies needed to determine N2O's effectiveness duration.

Evaluation of N-acetyl-ß-D-glucosaminidase as a prognostic marker for diabetic nephropathy in type 2 diabetics: systematic review and meta-analysis.

OBJECTIVE: This review aimed to assess the utility of urinary N-acetyl-ß-D-glucosaminidase (uNAG) as a prognostic biomarker for nephropathy in patients with type 2 diabetes mellitus. METHODS: The search for relevant studies was conducted across multiple databases, including PubMed (Medline), EMBASE, LILACS, CENTRAL, IBECS, and gray literature. We employed a random effects model to calculate the standardized mean difference and 95% confidence interval. Furthermore, we assessed heterogeneity using Cochrane's Q test and Higgins' I2 statistics. RESULTS: This review included a total of 16 articles involving 1669 patients, with 13 being case-control studies and three being cohorts. The meta-analysis conducted across all studies revealed significant heterogeneity. However, subgroup analysis of four studies indicated that an increase in uNAG among normoalbuminuric patients was associated with the development of macroalbuminuria (DMP = - 1.47; 95% CI = - 1.98 to 0.95; p < 0.00001; I2 = 45%). Conversely, it did not demonstrate effectiveness in predicting the development of microalbuminuria (DMP = 0.26; 95% CI = - 0.08 to 0.60; p = 0.13; I2 = 17%). CONCLUSIONS: Elevated uNAG levels in normoalbuminuric patients may indicate an increased risk for the development of macroalbuminuria, but not microalbuminuria. However, the high heterogeneity observed among the studies highlights the necessity for further research to validate these findings.

Enoxaparin improves COVID-19 by reducing Neutrophils Extracellular Traps (NETs) production.

BACKGROUND: COVID-19 causes consequences such as imbalance of the immune system and thrombotic events. During the infection process, NETs in excess induce a pro-inflammatory response and disseminated intravascular coagulation. We evaluated the role of enoxaparin as a potential inhibitor of NETs. METHODS: K18-hACE2 animals infected with the SARS-CoV-2 virus and a group of 23 individuals admitted to the hospital with COVID-19 treated with enoxaparin or without treatment and controls without the disease were included. RESULTS: Enoxaparin decreased the levels of NETs, reduced the signs of the disease and mitigated lung damage in the animals infected with SARS-CoV-2. These effects were partially associated with prevention of SARS-CoV-2 entry and NETs synthesis. Clinical data revealed that treatment with enoxaparin decreased the levels of inflammatory markers, the levels of NETs in isolated neutrophils and the organ dysfunction. CONCLUSION: This study provides evidence for the beneficial effects of enoxaparin in COVID-19 in addition to its anticoagulant role.

Biomarkers of neuropsychiatric dysfunction in intensive care unit survivors: a prospective cohort study.

OBJECTIVE: To assess factors associated with long-term neuropsychiatric outcomes, including biomarkers measured after discharge from the intensive care unit. METHODS: A prospective cohort study was performed with 65 intensive care unit survivors. The cognitive evaluation was performed through the Mini-Mental State Examination, the symptoms of anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale, and posttraumatic stress disorder was evaluated using the Impact of Event Scale-6. Plasma levels of amyloid-beta (1-42) [Aß (1-42)], Aß (1-40), interleukin (IL)-10, IL-6, IL-33, IL-4, IL-5, tumor necrosis factor alpha, C-reactive protein, and brain-derived neurotrophic factor were measured at intensive care unit discharge. RESULTS: Of the variables associated with intensive care, only delirium was independently related to the occurrence of long-term cognitive impairment. In addition, higher levels of IL-10 and IL-6 were associated with cognitive dysfunction. Only IL-6 was independently associated with depression. Mechanical ventilation, IL-33 levels, and C-reactive protein levels were independently associated with anxiety. No variables were independently associated with posttraumatic stress disorder. CONCLUSION: Cognitive dysfunction, as well as symptoms of depression, anxiety, and posttraumatic stress disorder, are present in patients who survive a critical illness, and some of these outcomes are associated with the levels of inflammatory biomarkers measured at discharge from the intensive care unit.

Coagulation biomarkers and coronavirus disease 2019 phenotyping: a prospective cohort study.

BACKGROUND: Because severe acute respiratory syndrome coronarivus 2 (SARS-CoV-2) leads to severe conditions and thrombus formation, evaluation of the coagulation markers is important in determining the prognosis and phenotyping of patients with COVID-19. METHODS: In a prospective study that included 213 COVID-19 patients admitted to the intensive care unit (ICU) the levels of antithrombin, C-reactive protein (CRP); factors XI, XII, XIII; prothrombin and D-dimer were measured. Spearman's correlation coefficient was used to assess the pairwise correlations between the biomarkers. Hierarchical and non-hierarchical cluster analysis was performed using the levels of biomarkers to identify patients´ phenotypes. Multivariate binary regression was used to determine the association of the patient´s outcome with clinical variables and biomarker levels. RESULTS: The levels of factors XI and XIII were significantly higher in patients with less severe COVID-19, while factor XIII and antithrombin levels were significantly associated with mortality. These coagulation biomarkers were associated with the in-hospital survival of COVID-19 patients over and above the core clinical factors on admission. Hierarchical cluster analysis showed a cluster between factor XIII and antithrombin, and this hierarchical cluster was extended to CRP in the next step. Furthermore, a non-hierarchical K-means cluster analysis was performed, and two phenotypes were identified based on the CRP and antithrombin levels independently of clinical variables and were associated with mortality. CONCLUSION: Coagulation biomarkers were associated with in-hospital survival of COVID-19 patients. Lower levels of factors XI, XII and XIII and prothrombin were associated with disease severity, while higher levels of both CRP and antithrombin clustered with worse prognosis. These results suggest the role of coagulation abnormalities in the development of COVID-19 and open the perspective of identifying subgroups of patients who would benefit more from interventions focused on regulating coagulation.

Biomarkers of neuropsychiatric dysfunction in intensive care unit survivors: a prospective cohort study / Biomarcadores de disfunção neuropsiquiátrica em sobreviventes de unidades de terapia intensiva: um estudo de coorte prospectivo

ABSTRACT Objective: To assess factors associated with long-term neuropsychiatric outcomes, including biomarkers measured after discharge from the intensive care unit. Methods: A prospective cohort study was performed with 65 intensive care unit survivors. The cognitive evaluation was performed through the Mini-Mental State Examination, the symptoms of anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale, and posttraumatic stress disorder was evaluated using the Impact of Event Scale-6. Plasma levels of amyloid-beta (1-42) [Aβ (1-42)], Aβ (1-40), interleukin (IL)-10, IL-6, IL-33, IL-4, IL-5, tumor necrosis factor alpha, C-reactive protein, and brain-derived neurotrophic factor were measured at intensive care unit discharge. Results: Of the variables associated with intensive care, only delirium was independently related to the occurrence of long-term cognitive impairment. In addition, higher levels of IL-10 and IL-6 were associated with cognitive dysfunction. Only IL-6 was independently associated with depression. Mechanical ventilation, IL-33 levels, and C-reactive protein levels were independently associated with anxiety. No variables were independently associated with posttraumatic stress disorder. Conclusion: Cognitive dysfunction, as well as symptoms of depression, anxiety, and posttraumatic stress disorder, are present in patients who survive a critical illness, and some of these outcomes are associated with the levels of inflammatory biomarkers measured at discharge from the intensive care unit.

RESUMO Objetivo: Avaliar os fatores associados aos desfechos neuropsiquiátricos de longo prazo, incluindo biomarcadores, medidos após a alta da unidade de terapia intensiva. Métodos: Foi realizado um estudo de coorte prospectivo com 65 sobreviventes de unidades de terapia intensiva. A avaliação cognitiva foi realizada por meio do Miniexame do Estado Mental; os sintomas de ansiedade e depressão foram avaliados por meio da Escala Hospitalar de Ansiedade e Depressão, e o transtorno de estresse pós-traumático foi avaliado pela Escala de Impacto do Evento-6. Os níveis plasmáticos de beta amiloide (1-42), beta amiloide (1-40), interleucina 10, interleucina 6, interleucina 33, interleucina 4, interleucina 5, fator de necrose tumoral alfa, proteína C-reativa e fator neurotrófico derivado do cérebro foram medidos na alta da unidade de terapia intensiva. Resultados: Das variáveis associadas à terapia intensiva, apenas o delirium foi relacionado de forma independente à ocorrência de comprometimento cognitivo de longo prazo. Além disso, níveis mais altos de interleucina 10 e interleucina 6 foram associados à disfunção cognitiva. Apenas a interleucina 6 foi associada de forma independente à depressão. A ventilação mecânica, os níveis de interleucina 33 e os níveis de proteína C-reativa foram associados de forma independente à ansiedade. Nenhuma variável foi associada de forma independente ao transtorno de estresse pós-traumático. Conclusão: A disfunção cognitiva, bem como os sintomas de depressão, ansiedade e transtorno de estresse pós-traumático, estão presentes em pacientes que sobrevivem a uma doença grave, e alguns desses desfechos estão associados aos níveis de biomarcadores inflamatórios medidos na alta da unidade de terapia intensiva.

A systematic review and meta-analysis of the accuracy of SARS-COV-2 IGM and IGG tests in individuals with COVID-19.

INTRODUCTION: Active SARS-CoV-2 infection is confirmed mainly through the detection of viral nucleic acid via the reverse transcriptase polymerase chain reaction (RT-PCR) technique. Methods to assess humoral responses contribute to the monitoring of the disease and confirmation of exposure to the virus. OBJECTIVE: To evaluate the accuracy of tests for IgM and IgG antibodies for SARS-CoV-2 infection confirmed by RT-PCR and utility as complementary data for immunosurveillance. METHODS: Literature research was performed by searching the terms "COVID-19", "COVID-19 diagnostic testing" and "test" in the databases MEDLINE, EMBASE, Cochrane Library, Web of Science and Cumulative Index to Nursing and Allied Health Literature to search for potentially eligible observational studies without language restrictions published up to September 2020. RESULTS: The pooled sensitivity and specificity, regardless of collection moment, was 80.0% (CI 95% 72.0-86.0) and 97.0% (CI 95% 94.0-98.0) for "IgM and/or IgG", respectively. Serology considering immunoglobulins M and G together had a high accuracy performance on "fifteenth day and after": sensitivity and specificity was 91.0% (CI 95% 85.0-94.0) and 98.0% (CI 95% 95.0-99.0) respectively, DOR 461 and AUC 0.98. CONCLUSION: This study shows that serology is a group of tests with high accuracy, mainly following the second week after infection.

Respiratory Outcomes After 6 Months of Hospital Discharge in Patients Affected by COVID-19: A Prospective Cohort.

Background: Considering millions of people affected by Coronavirus disease 2019 (COVID-19), long-lasting sequelae can significantly impact health worldwide. Data from prospective studies in lower-middle-income countries on persistent lung dysfunction secondary to COVID-19 are lacking. This work aims to determine risk factors and the impact of persistent lung dysfunctions in COVID-19 survivors. Methods: Observational and prospective cohort of patients admitted to a tertiary hospital from June 2020 to November 2020. Persistence of chest CT scan alterations, desaturation in the six-minute walk test (6MWT), forced expiratory volume in one second (FEV1), lung carbon monoxide diffusion (DLCO), and maximum inspiratory pressure (MIP) were measured 6 months after hospital discharge. Additionally, the Barthel index (BI) and the Modified Medical Research Council (mMRC) Dyspnea Scale were used to determine the impact of lung dysfunction in activities of daily living (ADL). Results: It was included 44 patients. Sixty percent had persistent lung CT scan abnormalities. From 18 to 43% of patients had at least one pulmonary function dysfunction, a decrease in FEV1 was the least prevalent (18%), and a reduction in DLCO and MIP was the most frequent (43%). In general, female gender, comorbidity index, and age were associated with worse lung function. Additionally, the presence of lung dysfunction could predict worse BI (r-square 0.28) and mMRC (r-square 0.32). Conclusion: Long-term lung dysfunction is relatively common in survivors from severe COVID-19 and impacts negatively on ADL and the intensity of dyspnea, similar to studies in high-income countries.

TsNTxP, a non-toxic protein from Tityus serrulatus scorpion venom, induces antinociceptive effects by suppressing glutamate release in mice.

Neuropathic pain is a common type of chronic pain caused by trauma or chemotherapy. However, this type of pain is undertreated. TsNTxP is a non-toxic protein isolated from the venom of the scorpion Tityus serrulatus, and it is structurally similar to neurotoxins that interact with voltage-gated sodium channels. However, the antinociceptive properties of this protein have not been characterized. The purpose of this study was to investigate the antinociceptive effects of TsNTxP in acute and neuropathic pain models. Male and female Swiss mice (25-30 g) were exposed to different models of acute pain (tail-flick test and nociception caused by capsaicin intraplantar injection) or neuropathic pain (chronic pain syndrome induced by paclitaxel or chronic constriction injury of the sciatic nerve). Hypersensitivity to mechanical or cold stimuli were evaluated in the models of neuropathic pain. The ability of TsNTxP to alter the release of glutamate in mouse spinal cord synaptosomes was also evaluated. The results showed that TsNTxP exerted antinociceptive effects in the tail-flick test to a thermal stimulus and in the intraplantar capsaicin administration model. Furthermore, TsNTxP was non-toxic and exerted antiallodynic effects in neuropathic pain models induced by chronic constriction injury of the sciatic nerve and administration of paclitaxel. TsNTxP reduced glutamate release from mouse spinal cord synaptosomes following stimulation with potassium chloride (KCl) or capsaicin. Thus, this T. serrulatus protein may be a promising non-toxic drug for the treatment of neuropathic pain.