The effect of curcumin on reserpine-induced depression-like behaviour in rats.

The aim of this study was to construct an animal model of depression that reproduces the human clinical manifestation, to evaluate the possible benefits of curcumin (CUR) in the treatment of depression and to compare its effect with the effect of a classic antidepressant, escitalopram (ESC). The behavior of depressive-like animals induced by administration of 1.5 mg/kg i. p. reserpine (R), during 10 days (n = 24) was evaluated via the open field test (OFT) and elevated plus maze (EPM) compared to control animals (n = 24) treated with carboxymethylcellulose (CMC) used as a vehicle. On the 11th day, each group was divided into 3 subgroups (n = 8): control (CMC), CMC+CUR, CMC+ESC for group without depression and CMC+R, CMC+R+CUR, CMC+R+ESC for group with depression. CUR (150 mg/kg i.p.) and ESC (20 mg/kg i.p.) were intraperitoneally administrated for 21 days. The improvement in depressive behaviour was assessed by OFT, EPM and biochemical analysis on the 32nd day. The results demonstrated that R induced hypomotility and increased oxidative stress in the brain, but also in the serum of rats. CUR had an antioxidant effect in the brain without significant effect on depressive-like behaviour while ESC improved the hypomotility of the depressive rats.

Hematological Parameters and Procalcitonin as Discriminants between Bacterial Pneumonia-Induced Sepsis and Viral Sepsis Secondary to COVID-19: A Retrospective Single-Center Analysis.

Bacterial and viral sepsis induce alterations of all hematological parameters and procalcitonin is used as a biomarker of infection and disease severity. Our aim was to study the hematological patterns associated with pulmonary sepsis triggered by bacteria and Severe Acute Respiratory Syndrome-Coronavirus-type-2 (SARS-CoV-2) and to identify the discriminants between them. We performed a retrospective, observational study including 124 patients with bacterial sepsis and 138 patients with viral sepsis. Discriminative ability of hematological parameters and procalcitonin between sepsis types was tested using receiver operating characteristic (ROC) analysis. Sensitivity (Sn%), specificity (Sp%), positive and negative likelihood ratios were calculated for the identified cut-off values. Patients with bacterial sepsis were older than patients with viral sepsis (p < 0.001), with no differences regarding gender. Subsequently to ROC analysis, procalcitonin had excellent discriminative ability for bacterial sepsis diagnosis with an area under the curve (AUC) of 0.92 (cut-off value of >1.49 ng/mL; Sn = 76.6%, Sp = 94.2%), followed by RDW% with an AUC = 0.87 (cut-off value >14.8%; Sn = 80.7%, Sp = 85.5%). Leukocytes, monocytes and neutrophils had good discriminative ability with AUCs between 0.76-0.78 (p < 0.001), while other hematological parameters had fair or no discriminative ability. Lastly, procalcitonin value was strongly correlated with disease severity in both types of sepsis (p < 0.001). Procalcitonin and RDW% had the best discriminative ability between bacterial and viral sepsis, followed by leukocytes, monocytes and neutrophils. Procalcitonin is a marker of disease severity regardless of sepsis type.

Coagulation Disorders in Sepsis and COVID-19-Two Sides of the Same Coin? A Review of Inflammation-Coagulation Crosstalk in Bacterial Sepsis and COVID-19.

Sepsis is a major cause of morbidity and mortality worldwide. Sepsis-associated coagulation disorders are involved in the pathogenesis of multiorgan failure and lead to a subsequently worsening prognosis. Alongside the global impact of the COVID-19 pandemic, a great number of research papers have focused on SARS-CoV-2 pathogenesis and treatment. Significant progress has been made in this regard and coagulation disturbances were once again found to underlie some of the most serious adverse outcomes of SARS-CoV-2 infection, such as acute lung injury and multiorgan dysfunction. In the attempt of untangling the mechanisms behind COVID-19-associated coagulopathy (CAC), a series of similarities with sepsis-induced coagulopathy (SIC) became apparent. Whether they are, in fact, the same disease has not been established yet. The clinical picture of CAC shows the unique feature of an initial phase of intravascular coagulation confined to the respiratory system. Only later on, patients can develop a clinically significant form of systemic coagulopathy, possibly with a consumptive pattern, but, unlike SIC, it is not a key feature. Deepening our understanding of CAC pathogenesis has to remain a major goal for the research community, in order to design and validate accurate definitions and classification criteria.

The outcome and risk factors associated with central and peripheral nervous system involvement in hospitalized COVID-19 patients: a retrospective cohort study.

Introduction: SARS-CoV-2 infection can affect any organ, including both the central nervous system (CNS) and peripheral nervous system (PNS). The aim of this study was to explore the outcome and risk factors associated with the involvement of either CNS or PNS in a cohort of hospitalized COVID-19 patients. Methods: We performed a retrospective observational cohort study of hospitalized adult patients with COVID-19, between May 2020 and December 2022, presenting with new onset neurological disabilities any time after admission. Results: We included 115 patients, 72 with CNS manifestations and 43 with PNS involvement. The CNS manifestations were COVID-19-associated encephalopathy, headache, neurovascular events, and seizures in 80.5, 43, 31.9, and 11.1% of patients, respectively. The neurovascular events were ischemic stroke in 17 (23.6%) patients, hemorrhagic stroke in 6 (8.3%) patients, venous thrombosis in 1 (1.4%) patient, and subarachnoid hemorrhage in 1 (1.4%) patient. Cranial nerve involvement was the most frequent PNS manifestation in 34 (79%) cases, followed by mononeuritis in 5 (11.6%) patients and polyneuropathy in 4 (9.3%) patients. The affected cranial nerves were the vestibulocochlear nerve in 26 (60.5%) patients, the olfactory nerve in 24 (55.8%) patients, the oculomotor nerves in 5 (11.6%) patients, and the facial nerve in 1 (2.3%) patient. Two patients (9.3%) presented with polyneuritis cranialis. Older age (HR = 1.02, 95% CI: 1.003-1.037, p = 0.01), COVID severity (HR = 2.53, 95% CI: 1.42-4.5, p = 0.002), ischemic cardiac disease (HR = 2.42, 95% CI: 1.05-5.6, p = 0.03), and increased D-dimers (HR = 1.00, 95% CI: 1.00-1.00, p = 0.02) were independently associated with the development of CNS manifestations. The factors associated with in-hospital mortality were age (HR = 1.059, 95% CI: 1.024-1.096, p = 0.001), C-reactive protein (HR = 1.006, 95% CI: 1.00-1.011, p = 0.03), CNS involvement (HR = 9.155, 95% CI: 1.185-70.74, p = 0.03), and leucocyte number (HR = 1.053, 95% CI: 1.026-1.081, p < 0.001). Conclusion: COVID-19-associated encephalopathy was the most common CNS manifestation in our study, but neurovascular events are also important considering the overlap between inflammatory and prothrombotic pathways, especially in severe cases. CNS involvement was associated with in-hospital all-cause mortality. PNS findings were various, involving mostly the cranial nerves, especially the vestibulocochlear nerve.

The Impact of the COVID-19 Pandemic on Inpatient Admissions for Psychotic and Affective Disorders: The Experience of a Large Psychiatric Teaching Hospital in Romania.

The COVID-19 pandemic resulted in a global sanitary crisis and, in addition, elicited serious mental health consequences. The utilization of psychiatric hospital-based services acts as an indicator of public mental health. Therefore, this research sought to investigate differences in the numbers and characteristics of inpatient admissions for psychotic and affective disorders at the largest Romanian psychiatric hospital between the period of lockdown (16 March−15 May 2020) and another three corresponding periods: the same year in the pre-lockdown period (16 January−15 March 2020), the immediate post-lockdown period (16 May−15 July 2020), and two years later (16 March−15 May 2022). A retrospective analysis was performed. The study included a total of 6604 patients. Inpatient admissions decreased during lockdown in comparison with the pre-lockdown period and immediate post-lockdown period for psychotic disorders (p < 0.001 and p < 0.001, respectively) and affective disorders (p < 0.001 and p < 0.001, respectively). For both psychotic and affective disorders, a decrease in the age of the patients admitted during lockdown, as compared with the pre-lockdown period (p < 0.05 and p < 0.001, respectively), was observed. The length of the hospital stay for affective disorders was higher immediately post-lockdown in comparison with the lockdown period (p < 0.001). Collectively, the present findings provide a glimpse of the immediate and long-term consequences of the COVID-19 pandemic and lockdown measures on patients' access to mental healthcare in the form of hospitalization, and these findings could provide the basis for the development of a different approach to times of crisis.

Development and Internal Validation of a New Prognostic Model Powered to Predict 28-Day All-Cause Mortality in ICU COVID-19 Patients-The COVID-SOFA Score.

Background: The sequential organ failure assessment (SOFA) score has poor discriminative ability for death in severely or critically ill patients with Coronavirus disease 2019 (COVID-19) requiring intensive care unit (ICU) admission. Our aim was to create a new score powered to predict 28-day mortality. Methods: Retrospective, observational, bicentric cohort study including 425 patients with COVID-19 pneumonia, acute respiratory failure and SOFA score ≥ 2 requiring ICU admission for ≥72 h. Factors with independent predictive value for 28-day mortality were identified after stepwise Cox proportional hazards (PH) regression. Based on the regression coefficients, an equation was computed representing the COVID-SOFA score. Discriminative ability was tested using receiver operating characteristic (ROC) analysis, concordance statistics and precision-recall curves. This score was internally validated. Results: Median (Q1−Q3) age for the whole sample was 64 [55−72], with 290 (68.2%) of patients being male. The 28-day mortality was 54.58%. After stepwise Cox PH regression, age, neutrophil-to-lymphocyte ratio (NLR) and SOFA score remained in the final model. The following equation was computed: COVID-SOFA score = 10 × [0.037 × Age + 0.347 × ln(NLR) + 0.16 × SOFA]. Harrell's C-index for the COVID-SOFA score was higher than the SOFA score alone for 28-day mortality (0.697 [95% CI; 0.662−0.731] versus 0.639 [95% CI: 0.605−0.672]). Subsequently, the prediction error rate was improved up to 16.06%. Area under the ROC (AUROC) was significantly higher for the COVID-SOFA score compared with the SOFA score for 28-day mortality: 0.796 [95% CI: 0.755−0.833] versus 0.699 [95% CI: 0.653−0.742, p < 0.001]. Better predictive value was observed with repeated measurement at 48 h after ICU admission. Conclusions: The COVID-SOFA score is better than the SOFA score alone for 28-day mortality prediction. Improvement in predictive value seen with measurements at 48 h after ICU admission suggests that the COVID-SOFA score can be used in a repetitive manner. External validation is required to support these results.

Dynamic Changes of the Neutrophil-to-Lymphocyte Ratio, Systemic Inflammation Index, and Derived Neutrophil-to-Lymphocyte Ratio Independently Predict Invasive Mechanical Ventilation Need and Death in Critically Ill COVID-19 Patients.

BACKGROUND: Hematological indices can predict disease severity, progression, and death in patients with coronavirus disease-19 (COVID-19). OBJECTIVES: To study the predictive value of the dynamic changes (first 48 h after ICU admission) of the following ratios: neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), monocyte-to-lymphocyte (MLR), systemic inflammation index (SII), and derived neutrophil-to-lymphocyte (dNLR) for invasive mechanical ventilation (IMV) need and death in critically ill COVID-19 patients. METHODS: Observational, retrospective, and multicentric analysis on 272 patients with severe or critical COVID-19 from two tertiary centers. Hematological indices were adjusted for confounders through multivariate analysis using Cox regression. RESULTS: Patients comprised 186 males and 86 females with no difference across groups (p > 0.05). ΔNLR > 2 had the best independent predictive value for IMV need (HR = 5.05 (95% CI, 3.06-8.33, p < 0.0001)), followed by ΔSII > 340 (HR = 3.56, 95% CI 2.21-5.74, p < 0.0001) and ΔdNLR > 1 (HR = 2.61, 95% CI 1.7-4.01, p < 0.0001). Death was also best predicted by an NLR > 11 (HR = 2.25, 95% CI: 1.31-3.86, p = 0.003) followed by dNLR > 6.93 (HR = 1.89, 95% CI: 1.2-2.98, p = 0.005) and SII > 3700 (HR = 1.68, 95% CI: 1.13-2.49, p = 0.01). CONCLUSIONS: Dynamic changes of NLR, SII, and dNLR independently predict IMV need and death in critically ill COVID-19 patients.

Neutrophil-to-Lymphocyte Ratio, a Novel Inflammatory Marker, as a Predictor of Bipolar Type in Depressed Patients: A Quest for Biological Markers.

(1) Background: Recent research suggests inflammation as a factor involved in the pathophysiology of mood disorders. Neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte (PLR), and systemic immune-inflammatory (SII) index ratios have been studied as peripheral markers of inflammation in bipolar and major depressive disorders. The purpose of this study is to comparatively analyze these inflammatory ratios among manic episodes of bipolar disorder, bipolar depression and unipolar depression. (2) Methods: 182 patients were retrospectively included in the study and divided into three groups: 65 manic patients, 34 patients with bipolar depression, and 83 unipolar depressive patients. White blood cells, neutrophils, monocytes, lymphocytes, and platelets were retrieved from the patients' database. NLR, MLR, PLR, and SII index were calculated using these parameters. (3) Results: Patients with manic episodes had elevated NLR (p < 0.001), MLR (p < 0.01), PLR (p < 0.05), and SII index (p < 0.001) compared to unipolar depression and increased NLR (p < 0.05) and SII index (p < 0.05) when compared to bipolar depression. NLR (p < 0.01) and SII index (p < 0.05) were higher in the bipolar depression than unipolar depression. NLR is an independent predictor of the bipolar type of depression in depressive patients. (4) Conclusions: The results confirm the role of inflammation in the pathophysiology of mood disorders and suggest the ability of NLR as a marker for the differentiation of bipolar from unipolar depression.