Clinical efficacy of high dose monotherapy of oral dihydroartemisinin in uncomplicated falciparum malaria in viet nam

The clinical efficacy of the monotherapy involving the administration of a high dose of dihydroartemisinin (DHA 900 mg) for 5 days was compared with that of the combination regimen (DHA 600 mg + mefloquine [MQ] 750 mg) in an open randomized study in 90 patients with uncomplicated falciparum malaria in the southern part of Viet Nam. Patients were randomly treated with the DHA-5 day monotherapy regimen (300, 300, 100, 100, and 100 mg given at 0, 24, 48, 72, and 96 h) or the DHA-MQ combination regimen (300 mg DHA at 0 h, then 300 mg DHA plus 750 mg MQ at 24 h). The end points for comparison were the parasite and fever clearance times (PCT and FCT) and recrudescence rates (by day 28 for DHA-5 days and day 42 for DHA-MQ). Eighty-nine patients completed the trial per protocol, including 45 cases receiving DHA-5 day and 44 receiving DHA-MQ. There was no difference in clinical manifestations, parasitemia density or other laboratory tests between the two patient groups. The PCTs were 35.3 +/- 17.4 h (mean +/- SD; range, 12-96) and 37.8 +/- 19.2 h (range, 12-96), respectively for the DHA-5 day and DHA-MQ regimens (P > 0.05). Twelve patients receiving the DHA-5 day regimen relapsed with falciparum malaria by day 28 (26.7%) and 5 patients receiving the DHA-MQ regimen relapsed by day 42 (11.4%) (P=0.07). Survival analysis showed that the DHA-5 day regimen had a radical cure rate significantly lower than that of the DHA-MQ regimen (P=0.003). The high dose of DHA in the monotherapy regimen did not increase the efficacy of the treatment of patients with uncomplicated Plasmodium falciparum malaria. The DHA combination regimens are suggested to be the better regimens for DHA.     

Atypical ovarian hyperthecosis in a virilized postmenopausal woman

Ovarian venous concentrations of testosterone (18.7 ng/mL and 8.2 ng/mL) were three to six times higher than the peripheral concentrations (2.8 ng/mL) in a hirsute postmenopausal woman. She had cystic hyperplasia of the endometrium and atypical hyperthecosis of the ovary. Postoperatively, the testosterone levels returned to normal. From the results of the immunoperoxidase reaction, the luteinized stromal cells of the ovaries were the site of increased production of the testosterone and estradiol. By the same technic, these cells were negative for LH but strongly positive for FSH. From these data, the authors conclude that the luteinized cells were the primary source of the excessive testosterone, that the same cells were the direct and indirect (by peripheral testosterone conversion) source of estradiol, that LH was very likely not involved in the process of steroid hormone production, and that FSH may be the trophic stimulus responsible for the functional activity of the luteinized stromal cells in this virilized postmenopausal woman.     

Resuscitation with normal saline (NS) vs. lactated ringers (LR) modulates hypercoagulability and leads to increased blood loss in an uncontrolled hemorrhagic shock swine model

BACKGROUND: Lactated ringers (LR) and normal saline (NS) are used interchangeably in many trauma centers. The purpose of this study was to compare the effects of LR and NS on coagulation in an uncontrolled hemorrhagic swine model. We hypothesized resuscitation with LR would produce hypercoagulability. METHODS: There were 20 anesthetized swine (35 +/- 3 kg) that underwent central venous and arterial catheterization, celiotomy, and splenectomy. After splenectomy blinded study fluid equal to 3 mL per gram of splenic weight was administered. A grade V liver injury was made and animals bled without resuscitation for 30 minutes. Animals were resuscitated with the respective study fluid to, and maintained, at the preinjury MAP until study end. Prothrombin Time (PT), Partial Thromboplastin Time (PTT), and fibrinogen were collected at baseline (0') and study end (120'). Thrombelastography was performed at 0'and postinjury at 30', 60', 90', and 120'. RESULTS: There were no significant baseline group differences in R value, PT, PTT, and fibrinogen. There was no significant difference between baseline and 30 minutes R value with NS (p = 0.17). There was a significant R value reduction from baseline to 30 minutes with LR (p = 0.02). At 60 minutes, R value (p = 0.002) was shorter while alpha angle, maximum amplitude, and clotting index were higher (p < 0.05) in the LR versus the NS group. R value, PT, and PTT were significantly decreased at study end in the LR group compared with the NS group (p < 0.05). Overall blood loss was significantly higher in the NS versus LR group (p = 0.009). CONCLUSIONS: This data indicates that resuscitation with LR leads to greater hypercoagulability and less blood loss than resuscitation with NS in uncontrolled hemorrhagic shock.     

Mediastinal hemangioma arising in setting of partial anomalous pulmonary venous drainage to azygous vein in a 57-year-old woman

Partial anomalous pulmonary venous drainage (PAPVD) to the azygous vein and benign posterior mediastinal hemangioma in adults are both rare entities in isolation. The coexistence of these two lesions in the same patient has not been reported. We describe a unique case of PAPVD to the azygous vein in an adult woman, where the anomalous left inferior pulmonary vein transited first through a large hemangioma, and then eventuated in the azygous vein.     

Argyrophilic, 'carcinoid-like' prostatic carcinoma. An immunocytochemical study

Four cases of argyrophilic or carcinoid-like prostatic carcinoma were studied immunocytochemically, using immunoperoxidase stains for prostatic-specific antigen, neuron-specific enolase, hydroxytryptamine (serotonin), somatostatin, and adrenocorticotropic hormone. All four showed strong positive reaction to prostatic-specific antigen and uniformly negative results with neuron-specific enolase, hydroxytryptamine, somatostatin, and adrenocorticotropic hormone. These findings lend further support to the concept that this particular prostatic tumor is truly a carcinoma that somehow manifests a carcinoid-like histomorphology, but does not possess evidence of true neuroendocrine or carcinoidal nature.     

Patient navigation across the cancer care continuum: An overview of systematic reviews and emerging literature

Patient navigation is a strategy for overcoming barriers to reduce disparities and to improve access and outcomes. The aim of this umbrella review was to identify, critically appraise, synthesize, and present the best available evidence to inform policy and planning regarding patient navigation across the cancer continuum. Systematic reviews examining navigation in cancer care were identified in the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, Cumulative Index of Nursing and Allied Health (CINAHL), Epistemonikos, and Prospective Register of Systematic Reviews (PROSPERO) databases and in the gray literature from January 1, 2012, to April 19, 2022. Data were screened, extracted, and appraised independently by two authors. The JBI Critical Appraisal Checklist for Systematic Review and Research Syntheses was used for quality appraisal. Emerging literature up to May 25, 2022, was also explored to capture primary research published beyond the coverage of included systematic reviews. Of the 2062 unique records identified, 61 systematic reviews were included. Fifty-four reviews were quantitative or mixed-methods reviews, reporting on the effectiveness of cancer patient navigation, including 12 reviews reporting costs or cost-effectiveness outcomes. Seven qualitative reviews explored navigation needs, barriers, and experiences. In addition, 53 primary studies published since 2021 were included. Patient navigation is effective in improving participation in cancer screening and reducing the time from screening to diagnosis and from diagnosis to treatment initiation. Emerging evidence suggests that patient navigation improves quality of life and patient satisfaction with care in the survivorship phase and reduces hospital readmission in the active treatment and survivorship care phases. Palliative care data were extremely limited. Economic evaluations from the United States suggest the potential cost-effectiveness of navigation in screening programs.     

Human cytochrome P450scc (CYP11A1) catalyzes epoxide formation with ergosterol

Cytochrome P450scc (P450scc) catalyzes the cleavage of the side chain of both cholesterol and the vitamin D(3) precursor, 7-dehydrocholesterol. The aim of this study was to test the ability of human P450scc to metabolize ergosterol, the vitamin D(2) precursor, and define the structure of the major products. P450scc incorporated into the bilayer of phospholipid vesicles converted ergosterol to two major and four minor products with a k(cat) of 53 mol · min(-1) · mol P450scc(-1) and a K(m) of 0.18 mol ergosterol/mol phospholipid, similar to the values observed for cholesterol metabolism. The reaction of ergosterol with P450scc was scaled up to make enough of the two major products for structural analysis. From mass spectrometry, NMR, and comparison of the NMR data to that for similar molecules, we determined the structures of the two major products as 20-hydroxy-22,23-epoxy-22,23-dihydroergosterol and 22-keto-23-hydroxy-22,23-dihydroergosterol. Molecular modeling and nuclear Overhauser effect (or enhancement) spectroscopy spectra analysis helped to establish the configurations at C20, C22, and C23 and determine the final structures of major products as 22R,23S-epoxyergosta-5,7-diene-3β,20α-diol and 3β,23S-dihydroxyergosta-5,7-dien-22-one. It is likely that the formation of the second product is through a 22,23-epoxy (oxirane) intermediate followed by C22 hydroxylation with the formation of strained 22-hydroxy-22,23-epoxide (oxiranol), which is immediately transformed to the more stable α-hydroxyketone. Molecular modeling of ergosterol into the P450scc crystal structure positioned the ergosterol side chain consistent with formation of the above products. Thus, we have shown that P450scc efficiently catalyzes epoxide formation with ergosterol giving rise to novel epoxy, hydroxy, and keto derivatives, without causing cleavage of the side chain.     

Cardiovascular risk assessment in persons with HIV infection in the developing world: comparing three risk equations in a cohort of HIV-infected Thais

Objective

There is growing concern regarding cardiovascular disease in HIV‐infected individuals in developing countries such as Thailand. We evaluated the 10‐year risk of coronary heart disease (CHD) in a Thai HIV‐infected cohort using three cardiovascular risk equations, and assessed the level of agreement among their predictions.

Methods

We carried out a cross‐sectional analysis of data on 785 Thai subjects followed prospectively in the HIV Netherlands Australia Thailand Collaboration (HIV‐NAT) cohort study from 1996 to 2009. Cardiovascular risk factor history, along with relevant laboratory and clinical data, was collected at follow‐up clinic visits. Ten‐year risks of CHD were calculated using the Framingham, Ramathibodi–Electricity Generating Authority of Thailand (Rama‐EGAT) and Data Collection on Adverse Effects of Anti‐HIV Drugs (D:A:D) risk equations.

Results

The mean age of the patients was 41.0 years; 55% of the subjects were male. The mean duration of antiretroviral therapy was 7.7 years. The prevalence of cardiovascular risk factors was low, with the most common risk factor being low high‐density lipoprotein (HDL) (36.3%). The prevalence of high cardiovascular risk scores (defined as 10‐year risk of CHD≥10%) was also low: 9.9, 2.1 and 0.8%, by the Framingham, Rama‐EGAT and D:A:D scoring systems, respectively. Only eight subjects (1.0%) had a history of CHD. Bland–Altman plots showed that the Framingham equation predicted a higher risk of CVD compared with the Rama‐EGAT and D:A:D equations, which agreed relatively well.

Conclusion

The predicted cardiovascular risk in this HIV‐infected Thai cohort was relatively low. The agreement among the Rama‐EGAT and D:A:D risk scores suggests that both equations may be appropriate estimators of cardiovascular risk in this population.