Continuous Renal Replacement Therapy in patients with HIV/AIDS

Background :AKI is a common complication among human immunodeficiency virus (HIV)--infecting patients and resulting in increased morbidity and mortality. CRRT is a useful method and instrument in critically ill patients with fluid overload and metabolic disarray, especially in those who are unable to tolerate the intermittent hemodialysis. However, the epidemiology, influence factors of CRRT and mortality in patients with HIV/AIDS are still unclear in China. This study aims to study the HIV-infected patients admitted in ICU and explore the influence factors correlated with CRRT and prognosis.Methods: We performed a retrospective case-control study, in ICU of Beijing Ditan Hospital Capital Medical University, which is a top three hospital majoring in infectious diseases. From June 1,2005 to May 31,2017, 225 cases were enrolled in this research eventually.Results: 122(54.2%) patients were diagnosed with AKI during their stay in ICU, the number and percentage of AKI stage 1/2/3 were respectively 38(31.1%)/23(18.9%)/61(50%). 26.2% of AKI patients received CRRT during the stay of ICU. 56.25% CRRT patients died in ICU. The 28-day mortality was 62.5%, and the 90-day mortality was 75%. By multivariate logistics analysis, it showed that the use of vasoactive agents (OR=174.31,95% CI 1.743-65.271, p=0.018), diagnosis of PCP(OR=27.136,95% CI 1.855-397.066, p=0.016) and longer duration of CRRT (OR=1.034,95% CI 1.004-1.065, p=0.028) were independent risk factors for predicting patients’ death of CRRT in ICU. The Cox Analysis for the cumulative survival of AKI 3 patients between the CRRT and non-CRRT groups shows no significant differences (p =0.309).Conclusions: The incidence of AKI was 54.2% in HIV-infected patients admitted to the ICU, and about 26.2% AKI patients received CRRT during the stay of ICU.56.25%CRRT patients died in ICU. The 28-day mortality was 62.5%, and the 90-day mortality was 75%. The use of vasoactive agents, diagnosis of PCP were independent risk factors for predicting patients’ death of CRRT in ICU. The cumulative survival of AKI 3 patients between CRRT and non-CRRT groups shows no significant differences.

CRRT in patients with HIV/AIDS

Background: AKI is a common complication among human immunodeficiency virus (HIV)--infecting patients and resulting in increased morbidity and mortality. CRRT is a useful method and instrument in critically ill patients with fluid overload and metabolic disarray, especially in those who are unable to tolerate the intermittent hemodialysis. However, the epidemiology, influence factors of CRRT and mortality in patients with HIV/AIDS are still unclear in China. This study aims to study the HIV-infected patients admitted in ICU and explore the influence factors correlated with CRRT and prognosis.Methods: We performed a retrospective case-control study, in ICU of Beijing Ditan Hospital Capital Medical University, which is a top three hospital majoring in infectious diseases. From June 1,2005 to May 31,2017, 225 cases were enrolled in this research eventually.Results: 122(54.2%) patients were diagnosed with AKI during their stay in ICU, the number and percentage of AKI stage 1/2/3 were respectively 38(31.1%)/23(18.9%)/61(50%). 26.2% of AKI patients received CRRT during the stay of ICU. 56.25% CRRT patients died in ICU. The 28-day mortality was 62.5%, and the 90-day mortality was 75%. By multivariate logistics analysis, it showed that the use of vasoactive agents (OR=174.31,95% CI 1.743-65.271, p=0.018), diagnosis of PCP(OR=27.136,95% CI 1.855-397.066, p=0.016) and longer duration of CRRT (OR=1.034,95% CI 1.004-1.065, p=0.028) were independent risk factors for predicting patients’ death of CRRT in ICU. The Cox Analysis for the cumulative survival of AKI 3 patients between the CRRT and non-CRRT groups shows no significant differences (p =0.309).Conclusions: The incidence of AKI was 54.2% in HIV-infected patients admitted to the ICU, and about 26.2% AKI patients received CRRT during the stay of ICU.56.25%CRRT patients died in ICU. The 28-day mortality was 62.5%, and the 90-day mortality was 75%. The use of vasoactive agents, diagnosis of PCP were independent risk factors for predicting patients’ death of CRRT in ICU. The cumulative survival of AKI 3 patients between CRRT and non-CRRT groups shows no significant differences.

Molecular Basis of the Leishmanicidal Activity of the Antidepressant Sertraline as a Drug Repurposing Candidate

ABSTRACTDrug repurposing affords the implementation of new treatments at a moderate cost and under a faster time-scale. Most of the clinical drugs againstLeishmaniashare this origin. The antidepressant sertraline has been successfully assayed in a murine model of visceral leishmaniasis. Nevertheless, sertraline targets inLeishmaniawere poorly defined. In order to get a detailed insight into the leishmanicidal mechanism of sertraline onLeishmania infantum, unbiased multiplatform metabolomics and transmission electron microscopy were combined with a focused insight into the sertraline effects on the bioenergetics metabolism of the parasite. Sertraline induced respiration uncoupling, a significant decrease of intracellular ATP level, and oxidative stress inL. infantumpromastigotes. Metabolomics evidenced an extended metabolic disarray caused by sertraline. This encompasses a remarkable variation of the levels of thiol-redox and polyamine biosynthetic intermediates, as well as a shortage of intracellular amino acids used as metabolic fuel byLeishmania. Sertraline killedLeishmaniathrough a multitarget mechanism of action, tackling essential metabolic pathways of the parasite. As such, sertraline is a valuable candidate for visceral leishmaniasis treatment under a drug repurposing strategy.

A CASE REPORT OF HEAT STROKE : AN ICEBERG

Heat stroke was first recognized by the Romans in 24 BC. But it took until 1946 for it to be shown that heat stroke could lead to multiorgan damage with hemorrhage and necrosis in the lungs, heart, liver, kidneys, brain and gut with a 10% to 50% mortality rate. Patients may present with neurological impairment of varying degrees and duration, including delirium, lethargy, coma and seizures, Neurological damage is presumably attributable to metabolic disarray, cerebral edema or ischemia. Here we are presenting a case of heat stroke, with coma due to neurological involvement who recovered functionally fully though with some residual damage revealed in computerized tomogram of the brain after conservative management of heat stroke.

Endogenous Melatonin Increases in Cerebrospinal Fluid of Patients after Severe Traumatic Brain Injury and Correlates with Oxidative Stress and Metabolic Disarray

Oxidative stress plays a significant role in secondary damage after severe traumatic brain injury (TBI); and melatonin exhibits both direct and indirect antioxidant effects. Melatonin deficiency is deleterious in TBI animal models, and its administration confers neuroprotection, reducing cerebral oedema, and improving neurobehavioural outcome. This study aimed to measure the endogenous cerebrospinal fluid (CSF) and serum melatonin levels post-TBI in humans and to identify relationships with markers of oxidative stress via 8-isoprostaglandin-F2α (isoprostane), brain metabolism and neurologic outcome. Cerebrospinal fluid and serum samples of 39 TBI patients were assessed for melatonin, isoprostane, and various metabolites. Cerebrospinal fluid but not serum melatonin levels were markedly elevated (7.28±0.92 versus 1.47±0.35 pg/mL, P<0.0005). Isoprostane levels also increased in both CSF (127.62±16.85 versus 18.28±4.88 pg/mL, P<0.0005) and serum (562.46±50.78 versus 126.15±40.08 pg/mL ( P<0.0005). A strong correlation between CSF melatonin and CSF isoprostane on day 1 after injury ( r=0.563, P=0.002) suggests that melatonin production increases in conjunction with lipid peroxidation in TBI. Relationships between CSF melatonin and pyruvate ( r=0.369, P=0.049) and glutamate ( r=0.373, P=0.046) indicate that melatonin production increases with metabolic disarray. In conclusion, endogenous CSF melatonin levels increase after TBI, whereas serum levels do not. This elevation is likely to represent a response to oxidative stress and metabolic disarray, although further studies are required to elucidate these relationships.

Polycystic ovarian syndrome: pathophysiology, molecular aspects and clinical implications

Polycystic ovarian syndrome (PCOS) is universally recognised as the commonest endocrinopathy of women. The definition and the aetiological hypotheses of PCOS are continuously evolving to accommodate expanding knowledge on the syndrome, which is now known to be more complex than purely a reproductive disorder. Increased androgen synthesis, disrupted folliculogenesis and insulin resistance lie at the pathophysiological core of PCOS. An intriguing concept involves the perpetuation of a vicious circle with endocrine/reproductive and metabolic components. An unfavourable metabolic environment may unmask genetic traits of ovarian dysfunction, and the unfolding endocrine derangement could further aggravate the metabolic disarray. This article reviews the molecular mechanisms known to underlie the ovarian and metabolic abnormalities characterising PCOS. The putative interdependence between reproductive and metabolic aspects of PCOS, and therapeutic implications for the management of PCOS, are also discussed.