Purpose of review
Artemisinin-based combination therapies (ACTs) have been deployed globally with remarkable success for more than 10 years without having lost their malaria treatment efficacy. However, recent reports from the Thai–Cambodian border reveal evidence of emerging resistance to artemisinins. The latest published clinical and molecular findings are summarized herein.
Recent findings
Clinical studies have identified delayed parasite clearance time as the most robust marker of artemisinin resistance. Resistance has only been documented from Southeast Asia and has been observed in isolates that show no significant decrease in drug susceptibility in vitro. Genetic investigations have yet to uncover robust molecular markers. In-vitro studies have identified parasite quiescence or dormancy mechanisms that protect early ‘ring-stage’ intra-erythrocytic parasites against short-term artemisinin exposure. This might be achieved by reducing the rate of hemoglobin degradation, important for artemisinin bioactivation.
Summary
Should ACTs fail, no suitable alternatives exist as first-line treatments of P. falciparum malaria. Intensified efforts are essential to monitor the spread of resistance, define therapeutic and operational strategies to counter its impact, and understand its molecular basis. Success in these areas is critical to ensuring that recent gains in reducing the burden of malaria are not lost.
Patients with tuberculosis admitted to the intensive care unit represent a small (1–3%) yet significant subset of the global tuberculosis burden. This article reviews current evidence supporting the diagnosis and management of patients with tuberculosis admitted to an intensive care unit from a combination of cohort studies and national and international tuberculosis guidelines. This review considers admission, diagnosis, mechanical ventilation, infection control, treatment and prognosis of patients with tuberculosis admitted to an intensive care unit. It highlights both diagnostic and management challenges and areas where ambiguity remains and further evidence is required.
Acute on chronic liver failure (ACLF) is a clinical syndrome characterised by acute hepatic decompensation, multi-organ failure and high mortality, in patients with cirrhosis. Organ dysfunction in ACLF is often reversible and when necessary these patients should be considered appropriate candidates for admission to an intensive care unit (ICU). The yearly increase in numbers of patients with ACLF admitted to ICU has been matched with an improvement in survival. ACLF has only been recently defined. In the absence of evidence-based guidelines we outline a systems-based approach to care which encompasses accepted ICU practice and evidence from trials in this cohort. We advocate for timely referral to specialist liver centres and consider the complexities of proceeding with liver transplantation. Equally, in a proportion of patients who continue to deteriorate, appropriate ceilings of care should be established. Future clinical trials may change treatment paradigms but care of patients with ACLF is undoubtedly becoming an integral part of an intensivist’s practice. We hope that this review is a welcome starting point when managing this complex clinical syndrome.
however dose reductions (DR) secondary to adverse effects (AE) are often required. The outcomes of MMF DR in OHT recipients have not yet been examined. We sought to determine the frequency of MMF DR within the first year post-OHT, and evaluate incidence of AE and biopsy-proven acute rejection (BPAR) in patients receiving full versus reduced dose MMF. Methods: Patients transplanted between May 2009 and October 2014 were retrospectively reviewed. MMF dose, rationale for dose change, and white blood cell counts (WBC) were recorded at time of hospital discharge, 3, 6, and 12 months post-OHT. Incidences of infection requiring treatment, leukopenia (WBC less than 3 cells/mm 3), gastrointestinal (GI) complaints (nausea, vomiting, diarrhea) and BPAR (≥ grade 2R/3A) were then correlated with MMF dose. Standard immunosuppression included tacrolimus and prednisone as well. Results: 86 patients were included in this study. The mean age at time of OHT was 56 ± 12 years; 76% of the patients were male. The mean MMF dose and WBC at discharge was 2470 ± 666 mg/day and 11 ± 4.3 cells/mm 3 , respectively. The mean MMF doses at month 3, 6, and 12 post-OHT were 1928 ± 920 mg/day, 1560 ± 984 mg/day, and 1560 ± 890 mg/day, respectively. At least one or more MMF DR occurred in 75/86 (87%) patients, with the highest percent DR between months 0 and 3. The primary indication for DR was leukopenia (60%). At 12 months, patients with persistent leukopenia required significantly lower mean MMF doses than those with transient leukopenia (467 ± 372 mg vs. 975 ± 325 mg, p= 0.0001). MMF DR occurred in 2 patients for GI complaints and in 11 patients due to infection. There were 6 incidences of ≥ 2R/3A rejection; 4 patients were on MMF 3 grams/day, 1 patient was on 2grams/day, and 1 patient was off MMF. Conclusion: Conventional MMF dosing of 3grams/day was poorly tolerated in our patients. When utilized as part of a standard immunosuppression regimen, a lower initial MMF dose may limit AE and decrease pill burden while still maintaining acceptable patient and graft outcomes. Further prospective studies are needed.
Whilst erythropoietin is working downstream from perivascular fat, it is possible that it may be therapeutically useful in obesity when hypoxia and inflammation reduce the normal activity of perivascular fat.
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