Imported Malaria in Portugal: A Retrospective Analysis from a Tertiary Public Hospital.

Most severe Plasmodium falciparum infections are experienced by young children. Severe symptoms are precipitated by vascular sequestration of parasites expressing a particular subset of the polymorphic P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion molecules. Parasites binding human endothelial protein C receptor (EPCR) through the CIDRα1 domain of certain PfEMP1 were recently associated with severe malaria in children. However, it has remained unclear to which extend the EPCR‐binding CIDRα1 domains epitomize PfEMP1 expressed in severe malaria. Here, we characterized the near full‐length transcripts dominating the var transcriptome in children with severe malaria and found that the only common feature of the encoded PfEMP1 was CIDRα1 domains. Such genes were highly and dominantly expressed in both children with severe malarial anaemia and cerebral malaria. These observations support the hypothesis that the CIDRα1‐EPCR interaction is key to the pathogenesis of severe malaria and strengthen the rationale for pursuing a vaccine or adjunctive treatment aiming at inhibiting or reducing the damaging effects of this interaction.

Clinical significance of serum lactate and lactate dehydrogenase levels for disease severity and clinical outcomes in patients with colorectal cancer admitted to the intensive care unit

Today world is trying to cope with the biggest pandemic caused by Coronavirus disease 2019 (COVID-19). The disease is graded as mild, moderate, serious and critical illness. Very few studies are done with methemoglobin along with other parameters for the assessment of the severity of COVID-19 disease. The objectives of the study were to estimate methemoglobin (Met-Hb), hemoglobin (Hb), ferritin and lactate dehydrogenase (LDH) levels in patients with COVID-19 disease and to investigate the interaction between these parameters and the severity of the disease. This observational study was conducted in three groups of COVID-19 patients- moderate, severe and critical, each group containing 30 patients, between June 2021 and September 2021 in the biochemistry department of a tertiary care hospital. For all patients, Met-Hb, Hb, ferritin, and LDH levels were estimated on the 2nd-3rd day of hospital admission. Patients in the critical group were older and had significantly high values of Met-Hb, ferritin and LDH and significantly low values of Hb (P<0.05). In multivariate ordinal regression analysis, older age (OR-3.08; 95%CI:1.19-7.19;P-0.019), higher values of LDH (OR-8.66; 95%CI:2.53-29.5; P-0.001) and ferritin (OR-3.08; 95%CI:1.09-8.7;P-0.033) were independently associated with severity of the disease. A cut-off value of 410.50 U/L for LDH predicted the severity of the disease with 90% sensitivity and 88.3% specificity. In conclusion, higher levels of LDH and ferritin were related to the severity of the disease in COVID-19 cases. Although Met-Hb showed a minimal increase without any association with severity, it may be an underlying cause of hypoxia that may go unnoticed. So, monitoring of all these parameters should be done at intervals.

Lactate dehydrogenase (LDH), a nonspecific inflammatory biomarker, has been used in the assessment of acute myocardial infarction, acute hepatitis, acute lung injury, and other severe diseases. However, no studies have evaluated the prognostic value of LDH in patients with non-traumatic intracerebral hemorrhage (ICH). This cohort study aims to assess the association between LDH levels and 28-day all-cause mortality in patients with non-traumatic ICH. Data for this retrospective cohort analysis were obtained from the MIMIC-IV (v2.2) database, and the study included patients with non-traumatic ICH as defined by the International Classification of Diseases, 9th and 10th editions. Patients were categorized into four distinct groups based on their LDH levels. The primary outcome of interest was the 28-day mortality rate. To analyze these associations and assess the consistency of interactions, subgroup analyses, Cox regression analysis, Kaplan–Meier (K–M) curves, and nonlinear analysis were conducted. A total of 406 patients with non-traumatic ICH were enrolled in the study and were divided into quartiles based on LDH levels. The K–M curve indicated that the 28-day all-cause mortality rate of patients in the Q4 group (LDH > 287.25) was significantly higher than in the Q1 (LDH < 194.7) (P < 0.001) and Q2 (194.7 < LDH < 233.0) (P < 0.001) groups, though not significantly different from Q3 (P ═ 0.140). Multivariate Cox proportional hazards analysis revealed that patients in the highest LDH quartile had a significantly increased risk of mortality compared to those in the lowest quartile across three models: unadjusted [HR, 3.401; 95% CI, 1.719–6.731; P < 0.001], partially adjusted [HR, 2.422; 95% CI, 1.211–4.846; P ═ 0.012], and fully adjusted [HR, 3.054; 95% CI, 1.522–6.126; P ═ 0.002]. Restricted cubic spline (RCS) models revealed an L-shaped association between LDH levels and the 28-day all-cause mortality rate, indicating a nonlinear relationship (P < 0.001). No significant interactions were observed between LDH levels and other factors in the subgroup analyses (all P for interaction > 0.05). Our findings indicate a significant association between 28-day all-cause mortality and LDH levels in patients with non-traumatic ICH. Specifically, patients with elevated LDH levels within the first 24 h of ICU admission are at a higher risk of mortality.

BackgroundIn developing countries where Plasmodium falciparum malaria is endemic, viral encephalitis and cerebral malaria are found in the same population, and parasitemia with Plasmodium falciparum is common in asymptomatic children. The objective of this study was to investigate the cerebrospinal fluid (CSF) biochemistry in children with cerebral malaria compared to those with presumed viral encephalitis.MethodsWe studied the following CSF parameters: cell count, glucose, protein, lactic dehydrogenase (LDH) and adenosine deaminase (ADA) levels, in children with cerebral malaria, with presumed viral encephalitis, and in control subjects who had a lumbar puncture after a febrile convulsion with postictal coma.ResultsWe recruited 12 children with cerebral malaria, 14 children with presumed viral encephalitis and 20 controls prospectively, over 2 years in the Government General Hospital in Kakinada, India. Patients with cerebral malaria had significantly lower CSF glucose, and higher protein, LDH, CSF/blood LDH ratio and CSF ADA levels but a lower CSF/serum ADA ratio compared to controls (p < 0.01). Patients with cerebral malaria had lower CSF white cell count, glucose, protein, LDH levels and CSF/serum ADA ratio compared to patients with presumed viral encephalitis. CSF/serum ADA ratio was lower in patients with cerebral malaria due to the fact that serum ADA levels were significantly higher in patients with cerebral malaria compared to the other two groups. A CSF/serum ADA ratio of <0.38 and a CSF glucose level of <3.4 mmol/l were selected as the cut-off values with the highest sensitivities and specificities for comparing the two conditions.ConclusionCSF/serum ADA ratio and CSF glucose levels were the best discriminators of cerebral malaria from presumed viral encephalitis in our study. Further studies are needed to explore their usefulness in epidemiological studies.

Biomarkers for Risk Stratification in Patients With Type A Acute Aortic Dissection

The impact of HIV infection on malaria is unclear in nonendemic areas. In endemic territories, HIV has been reported to be a risk factor for higher morbidity. Nowadays, as HIV-infected patients travel more, it is important to assess the impact of HIV at the individual level on imported malaria. This retrospective case-control study collected data on HIV-infected patients diagnosed with malaria (2000-2017) and matched them with two controls based on age, sex and ethnicity. Clinical and biological parameters were collected and compared. We identified 47 cases and matched them with 94 controls. Comparing each of the WHO 2014 severity criteria, hyperparasitemia above 10% (P = 0.006; 12.8 versus 1.1%), icterus (P = 0.042; 14.9 versus 4.3%), acute renal failure (P = 0.022; 25.5 versus 9.6%) and bacteraemia (P = 0.014; 6.4 versus 0%) were significantly more present in HIV-infected patients with a trend to more cerebral malaria (12.8 versus 6.4%). HIV- infected patients were hospitalized more frequently and for longer periods. We observed a higher number of severity criteria when CD4 T-cell count was lower, especially below 200 cells/μl. The difference in occurrence of severe malaria disappeared when patients with CD4 T-cell count more than 500 cells/μl and undetectable viral load (n = 9) were compared with controls. De-novo HIV diagnosis was made during the malaria episode in 17% of cases. HIV infection has an impact on the imported malaria profile, although it is unclear whether well controlled HIV-infected patients have a higher risk of severe malaria. HIV-infected patients should be particularly targeted for pretravel advice.

Background: The recent coronavirus pandemic caused systemic human disease that killed many people worldwide, and we are still witnessing the resulting conflicts. Lactate dehydrogenase (LDH) and Creatine phosphokinase (CPK), markers of muscle damage, are potentially associated with a more severe Coronavirus disease (COVID-19). This study aims to evaluate the association between elevated LDH and CPK with severity and mortality in COVID-19 patients. Methods: A retrospective single-center study that included 282 patients with COVID-19 was conducted between 2020-2021 (in Four disease waves) in Rouhani Hospital, Babol, Mazandaran (Northern Iran). Data were extracted from the medical records of all consecutive patients and followed up until death or till 9 September 2021. Univariate and multivariate Cox regression analyses were performed to investigate the associated factors with in-hospital mortality and disease severity. Additionally, logistics regression analyses and Kaplan-Meier curves were used to determine the association between LDH and CPK levels and the prognosis of COVID-19 patients. Results: The mean age of patients was 60.21 years, and the disease was severe in 31.2% of patients. About 39 (13.8%) patients died during hospitalization and 20 during the follow-up (280.63 ± 192.85 days). Significantly higher in-hospital mortality among older age patients was observed (p = 0.025), including those admitted in the first COVID wave (p = 0.015), those having longer hospital admission (p = 0.008), patients with severe disease (p &lt; 0.001), higher LDH (p = 0.004), higher CPK (p = 0.017), those needing ICU admission (p &lt; 0.001), needing NIV (p = 0.002), and those needing IMV (p &lt; 0.001). In other words, the severity of COVID-19 was significantly associated with older age (p &lt; 0.001), patients with CVDs (p &lt; 0.001), HTN (p = 0.002), DM (p = 0.02), the duration of hospital stays (p = 0.015), ICU admission (p = 0.009), need for NIV (p = 0.003), IMV (p &lt; 0.001), and mortality in long-term follow-up (p = 0.006). However, LDH (p = 0.417) and CPK levels (p = 0.091) were not significantly related to disease severity. LDH levels had a significant effect on hospitalization (p &lt; 0.001, 95%CI= 1.877 to 8.675, HR= 4.036), short-term (p = 0.011, 95%CI= 1.202 to 4.209, HR= 2.249) and long-term (p = 0.002, 95%CI= 1.427 to 4.738, HR= 2.601) mortality, as well as the length of hospital stay until intensive care unit (ICU) admission (p = 0.017, 95%CI= 1.186 to 5.490, HR= 2.551). Receiver operating characteristic curve analysis demonstrated an optimal cutoff point of LDH in the first, third, and fourth waves greater than or equal to 759.53 IU/L, 818.52 IU/L, and 840.92 IU/L, respectively. The test sensitivities were 61.1%,66.7%, and 75%, respectively; specificities were 88.2%,76.6%, and 79.7%, respectively; the AUCs were 0.722, 0.786, and 0.720, respectively, among all hospitalized patients. Comparing the areas under fitted ROC curves, serum LDH was significantly associated with mortality (p &lt; 0.05 for the mentioned cut-off points). However, the area under the curve was not significant at the aforementioned points found for CPK (p &gt; 0.05 for CPK at all waves). Conclusion: Higher levels of LDH, unlike CPK, significantly predicted severity during hospitalization and mortality in different time periods. Also, its sensitivity increased in new waves. When the COVID-19 patient is hospitalized, these results can help determine the appropriate diagnostic test.

Homeless people hospitalized with COVID-19 in Brussels

may present in its most severe forms. 2,5,6,8 Despite a vigorous program of malaria control in the Kingdom of Saudi Arabia, the infection is still endemic in the southwestern area of the country. 9 As a result of continued preventive measures, the epidemiology of the disease may be changing, and the proportion of nonimmune individuals may increase. Furthermore, the emergence of chloroquine-resistant malaria in the neighboring country of Yemen has a major implication for the Gizan population. 2,4 The frequency and clinical outcome of severe malaria may provide useful, albeit indirect, information on the emergence of antimalarial drug resistance in this region. We describe the clinicopathologic profile and mortality in patients treated for severe malaria in King Fahad Central Hospital (KFCH), Gizan, Saudi Arabia.

To identify the main clinical and laboratory features of disseminated histoplasmosis (DH) in human immunodeficiency virus (HIV) patients and compare them with those of HIV patients with other opportunistic diseases. Retrospective study of HIV patients comparing the clinical and laboratory data of patients with and without DH. Univariate and multivariate analyses were performed to verify the risk factors related to DH. In total, 378 HIV patients were included, 164 with DH and 214 with other opportunistic diseases. Acute renal failure, respiratory insufficiency and septic shock were more frequent in DH patients, who also had a higher mortality (32%vs. 14%, P < 0.001). Independent risk factors for DH were: acute renal failure [odds ratio (OR) 5.2; 95% confidence interval (CI) 3.2-8.5; P < 0.001], splenomegaly (OR 3.4; 95% CI 1.19-9.9; P < 0.001), respiratory insufficiency (OR 2.7 95% CI 1.5-5.0; P < 0.001), proteinuria (OR 2.7; 95% CI 1.3-5.2; P = 0.03), hypotension (OR 2.5; 95% CI 1.2-5.0; P = 0.008), hepatomegaly (OR 2.4; 95% CI 1.2-4.8; P = 0.01), cutaneous lesions (OR, 1.9; 95% CI 1.0-3.3; P = 0.02) and weight loss (OR 1.8; 95% CI 1.0-3.1; P = 0.03). Our results suggest that DH is a severe opportunistic disease with high mortality rate, which should be promptly recognized in order to provide early specific treatment.

COVID-19 is a dangerous disease with long-lasting consequences. Vaccination contributes to the accumulation of neutralizing anti-S IgG antibodies, reducing the incidence of COVID-19 and its complications. However, in some individuals, the inflammatory process can persist for an indefinite period and lead to a wide range of dysfunctions. The current task is to investigate molecular markers for their detection. The aim of this study is to examine the levels of anti-S IgG antibodies, lactate, glucose, lactate dehydrogenase, and C-reactive protein in the peripheral blood of individuals who have and have not been affected by COVID-19 after vaccination. The research subject is venous blood. Among 547 employees of the Neurosurgery Institute (481 vaccinated against COVID-19 and 66 unvaccinated individuals), levels of anti-S IgG antibodies were investigated, as well as levels of lactate, lactate dehydrogenase, glucose, and C-reactive protein. At the time of the study, among 372 individuals, 16 months had passed from the first vaccination, and 12 months had passed from the second vaccination; in 21 individuals, 12 months had passed after a single vaccination, and in 88 individuals, 16 months had passed from the first vaccination, 12 months from the second, and 6 months from the third vaccination. Methods. Quantitative determination of IgG antibodies to the S protein of the SARS-CoV-2 virus. Confirmation of COVID-19 using the RT-PCR method (Allplex 2019-nCoV kit, SeeGene, Korea). Levels of lactate, lactate dehydrogenase, glucose, and C-reactive protein were determined using reagents from BioSystems (Spain). Statistical analysis of the obtained data was performed using Jamovi software (USA) and the following criteria: χ2 ‒ Kruskal-Wallis, W ‒ Dwass-Steel-Critchlow-Fligner (DSCF), χ2 ‒ Pearson, t ‒ Student, rs ‒ Spearman, τb ‒ Kendall. A statistically significant difference was considered at p &lt; 0.05. Results. The level of anti-S IgG antibodies to the SARS-CoV-2 virus was higher in vaccinated individuals compared to unvaccinated individuals (Kruskal-Wallis χ2=14.09; p &lt; 0.001). A higher level of antibodies to the S protein of the virus was observed when using the Comirnaty vaccine compared to vaccination with Moderna, AstraZeneca, Pfizer, and CoronaVac (Dwass-Steel-Critchlow-Fligner (DSCF): W 4.26, p=0.002; W 4.62, p=0.010; W 4.84, p=0.006, respectively). Vaccination reduces the likelihood of contracting the disease by 1.84 times (Odds Ratio (OR) 1.84; 95% Confidence Interval (CI) 1.02‒3.30; χ2=4.129; p=0.043). However, no statistically significant dependence on the prevention of COVID-19 incidence based on the type of vaccines used was found (Kruskal-Wallis χ2=2.072; p=0.72). A statistically significant difference in C-reactive protein levels is observed between groups with early mild complications and early moderate-severity complications (DSCF: W=4.193, p=0.009). A statistically significant difference in LDH levels is noted between individuals without chronic diseases and those with chronic diseases at the time of the study (Kruskal-Wallis χ2=6.08, p=0.014). In individuals vaccinated against the SARS-CoV-2 virus, a positive correlation is found between the levels of C-reactive protein and lactate dehydrogenase (Kendall's τb 0.134, p &lt; 0.001). The mean levels of lactate among individuals with mild, moderate, and severe forms of COVID-19 are higher than the reference mean; similarly, the mean levels of glucose in these same groups are higher than the reference mean. A positive correlation exists between the levels of lactate and glucose among individuals vaccinated against the SARS-CoV-2 virus (Kendall's τb 0.082, p &lt; 0.01). Conclusions. Vaccination contributes to an increase in antibody levels. The level of antibodies after the third vaccination exceeded the levels after the first (Dwass-Steel-Critchlow-Fligner (DSCF): W 4.42, p=0.005) and second vaccinations (W 4.24, p=0.008). Vaccination reduces the likelihood of COVID-19 infection by 1.84 times (Odds Ratio ‒ 1.84; 95% Confidence Interval 1.02‒3.30; Pearson χ2=4.129; p=0.043). The frequency of COVID-19 incidence is not dependent on the type of vaccine used: AstraZeneca, Comirnaty, CoronaVac, Moderna, Pfizer (Kruskal-Wallis χ2=2.072; p=0.723), and the level of antibodies in the vaccinated individuals' serum. In the post-COVID-19 remote period, regardless of vaccination status, various complications are observed. However, among the vaccinated, the number of individuals without complications or with minimal complications is greater than in the unvaccinated group, while the number of individuals with early and severe complications is lower (Kruskal-Wallis χ2=6.127; p=0.047). A high level of C-reactive protein (DSCF: W=4.19, p=0.009), a tendency toward increased levels of lactate dehydrogenase (DSCF: W=3.27, p=0.054), elevated levels of lactate (2.17+1.23, t=3.34; p=0.002), and glucose (6.06+0.048, t=10.54; p &lt; 0.001) indicate that after recovering from COVID-19, regardless the type of vaccines used, in individuals with distant symptoms there are metabolic changes that are signs of a chronic inflammatory process. Individuals with chronic diseasees show an increase in the level of lactate dehydrogenase (χ2=6.08; p=0.014) and a tendency toward increased levels of C-reactive protein (χ2=3.74; p=0.053). Molecular markers of inflammation such as increased levels of lactate, glucose, C-reactive protein, and lactate dehydrogenase are informative for identifying individuals with an inflammatory process in the post-COVID-19 remote period.

560P - Impact of Pre-Treatment Lactate Dehydrogenase (Ldh) Levels on Prognosis and Bevacizumab Efficacy in Advanced Colorectal Cancer Patients

BackgroundOne of the most prevalent medical issues observed during pregnancy is hypertension. Hypertensive disorders of pregnancy (HDP) and their consequences affect around 5-10% of all pregnancies globally. Preeclampsia is caused by endothelial dysfunction, which causes widespread endothelial leakage and contributes to potentially fatal consequences, such as eclampsia, placental abruption, disseminated intravascular coagulation (DIC), severe renal failure, pulmonary edema, and hepatocellular necrosis. As a result, looking for predictive markers for at-risk pregnancies that can suggest poor maternal or fetal outcomes is critical. Elevated levels of lactate dehydrogenase (LDH), as a sign of cellular damage and dysfunction, can be utilized as a biochemical marker in pregnancy-induced hypertension (PIH) as it represents the severity of the disease, and the occurrence of problems, and has also been demonstrated to co-relate with fetomaternal outcomes.MethodologyA total of 230 singleton pregnant women of 28-40 weeks of gestational age were enrolled in this study. All women were divided into two groups - normotensive and preeclamptic-eclamptic groups; the second group was further divided into mild preeclampsia, severe preeclampsia, and eclampsia, based on blood pressure and the presence of proteinuria. Serum lactate dehydrogenase levels were measured in both groups and correlated with their fetomaternal outcome.ResultsMean serum lactate dehydrogenase (LDH) level in eclamptic women was 1515.86 ± 754, in severely preeclamptic women was 932.2 ± 448, mild preeclamptic women were 580.5±213, while in normotensive women mean LDH level was 378.6 ± 124. The difference between normotensive and preeclamptic-eclamptic women was statistically significant (p < 0.001). The complications in the preeclamptic-eclamptic group were increased significantly in women with LDH > 800 IU/L, 600-800 IU/L compared to those who had < 600 IU/L LDH levels.ConclusionsSerum LDH levels were significantly higher in women of preeclamptic-eclamptic group compared to the normotensive pregnant women. Higher LDH levels were positively correlated with disease severity and maternal complications like placental abruption, hemolysis elevated liver enzymes low platelet count (HELLP), disseminated intravascular coagulation (DIC), acute renal failure, intracranial hemorrhage, pulmonary edema, and maternal death and for fetal complications like preterm, intrauterine growth restriction (IUGR), APGAR at 1 minute < 7, APGAR at 5 minutes < 7, low birth weight (LBW), neonatal intensive care unit (NICU) admission and intrauterine fetal death (IUFD).

Objective To investigate lactate dehydrogenase (LDH) level in serum of patients with advanced non-small cell lung cancer (NSCLC) before and after chemotherapy and the relationship of it with efficacy of chemotherapy and disease progression. Methods 57 patients with advanced NSCLC received standard first-line chemotherapy and some patients received second-line chemotherapy. The lung CT imaging changes were observed before and after chemotherapy. The serum LDH level was monitored during chemotherapy. The changes of serum LDH level and its relationship with efficacy of chemotherapy and disease progression were analyzed. Results The serum LDH level in patients with NSCLC was significantly higher than that in the normal. After first-line chemotherapy, the remissive group showed decreased LDH level, and the progressive group showed increased LDH level. LDH level in tumor recurrence was significantly higher than that in remissive period. After second-line chemotherapy for the progressive patients, the remissive group also showed decreased LDH level, and the progressive group showed increased LDH level. Conclusions Serum LDH level may reflect chemotherapy efficacy of lung cancer,and can be used to monitor recurrence of lung cancer. Key words: Lung cancer; Chemotherapy; Lactate dehydrogenase