Correction: Intravenous therapy duration and outcomes in melioidosis: a new treatment paradigm.
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ABSTRACT:
SUBMITTER: PLOS Neglected Tropical Diseases Staff
PROVIDER: S-EPMC4406616 | biostudies-other | 2015 Apr
REPOSITORIES: biostudies-other
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Project description:BackgroundInternational melioidosis treatment guidelines recommend a minimum 10 to 14 days' intravenous antibiotic therapy (intensive phase), followed by 3 to 6 months' oral therapy (eradication phase). This approach is associated with rates of relapse, defined as recurrence following the eradication phase, that can exceed 5%. Rates of recrudescence, defined as recurrence during the eradication phase, have not previously been reported. In response to low eradication phase completion rates in Australia, a local guideline has evolved over the last ten years recommending a longer minimum intensive phase duration for many cases of melioidosis.Methodology/ principal findingsThis retrospective cohort study reviews antibiotic duration for the first episode of care for all patients diagnosed with melioidosis and surviving the intensive phase during a recent three year period in the tropical north of Australia's Northern Territory; we also review adherence to the current local guideline and treatment outcomes. Of 215 first episodes of melioidosis surviving the intensive phase, the median (interquartile range) intensive phase duration was 26 (14-34) days. One hundred and eight (50.2%) patients completed eradication therapy; 58 (27.0%) patients took no eradication therapy. At 28 months' follow-up, one (0.5%) relapse and eleven (5.1%) recrudescences had occurred. On exact logistic regression analysis, the only independent risk factors for recrudescence were self-discharge during the intensive phase (odds ratio 6.2 [95% confidence interval 1.2-30.0]) and septic shock (odds ratio 5.3 [95% confidence interval 1.1-25.7]).Conclusions/ significanceRelapsed melioidosis is rare in patients who receive a minimum intensive phase duration specified by our guideline and extended according to clinical progress. Recrudescence rates may improve with reductions in rates of self-discharge. Given the low relapse rate despite a high rate of eradication therapy non-adherence, the duration and necessity of eradication therapy for different patients after guideline-concordant intensive therapy should be evaluated further.
| S-EPMC4374799 | biostudies-literature
Project description:After 3 decades of clinical trials, repeated proof-of-concept success has now been demonstrated in hemophilia A and B gene therapy. Current clinical hemophilia gene therapy efforts are largely focused on the use of systemically administered recombinant adeno-associated viral (rAAV) vectors for F8 or F9 gene addition. With multiple ongoing trials, including licensing studies in hemophilia A and B, many are cautiously optimistic that the first AAV vectors will obtain regulatory approval within approximately 1 year. While supported optimism suggests that the goal of gene therapy to alter the paradigm of hemophilia care may soon be realized, a number of outstanding questions have emerged from clinical trial that are in need of answers to harness the full potential of gene therapy for hemophilia patients. This article reviews the use of AAV vector gene addition approaches for hemophilia A and B, focusing specifically on information to review in the process of obtaining informed consent for hemophilia patients prior to clinical trial enrollment or administering a licensed AAV vector.
| S-EPMC8877054 | biostudies-literature
Project description:In treatments of solid tumors, adoptive transfer of ex vivo expanded natural killer (NK) cells has dawned as a new paradigm. Compared with cytotoxic T lymphocytes, NK cells take a unique position targeting tumor cells that evade the host immune surveillance by down-regulating self-antigen presentation. Recent findings highlighted that NK cells can even target cancer stem cells. The efficacy of allogeneic NK cells has been widely investigated in the treatment of hematologic malignancies. In solid tumors, both autologous and allogeneic NK cells have demonstrated potential efficacy. In allogeneic NK cell therapy, the mismatch between the killer cell immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA) can be harnessed to increase the antitumor activity. However, the allogeneic NK cells cause more adverse events and can be rejected by the host immune system after repeated injections. In this regard, the autologous NK cell therapy is safer. This article reviews the published results of clinical trials and discusses strategies to enhance the efficacy of the NK cell therapy. The difference in immunophenotype of the ex vivo expanded NK cells resulted from different culture methods may affect the final efficacy. Furthermore, currently available standard anticancer therapy, molecularly targeted agents, and checkpoint inhibitors may directly or indirectly enhance the efficacy of NK cell therapy. A recent study discovered that NK cell specific genetic defects are closely associated with the tumor immune microenvironment that determines clinical outcomes. This finding warrants future investigations to find the implication of NK cell specific genetic defects in cancer development and treatment, and NK cell deficiency syndrome should be revisited to enhance our understanding. Overall, it is clear that NK cell therapy is safe and promises a new paradigm for the treatment of solid tumors.
| S-EPMC6826624 | biostudies-literature
Project description:The majority of patients with B-cell non-Hodgkin lymphoma (NHL) can be cured with standard chemoimmunotherapy. However, patients who fail first line therapy have dismal outcomes, particularly if they have disease that is resistant to salvage therapy, including chemoimmunotherapy, radiation and/or autologous stem cell transplantation. Indolent B-NHLs, such as follicular lymphoma (FL), although not generally considered curable may be treated over many years with good prognosis. However, a subset of B-NHLs can undergo histologic transformation into more aggressive subtypes with outcomes similar to aggressive B-NHLs. In recent years, T cells genetically modified with chimeric antigen receptors (CARs), have demonstrated a remarkable capacity to induce complete and durable clinical responses in patients with chemotherapy-refractory lymphomas. Indeed, two autologous CD19-directed CAR-modified T cell products have now been FDA-approved for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL) and transformed FL, while a plethora of other CAR-T cell targets are being explored in ongoing clinical trials. The purpose of this review is to summarize the clinical efficacy and unique toxicities of individually developed CAR-T cell products for the treatment of lymphomas, and their evolution from the laboratory bench to commercialization.
| S-EPMC6880960 | biostudies-literature
Project description:BACKGROUND:Progressive lung damage from recurrent exacerbations is the major cause of mortality and morbidity in cystic fibrosis. Life expectancy of people with cystic fibrosis has increased dramatically in the last 40 years. One of the major reasons for this increase is the mounting use of antibiotics to treat chest exacerbations caused by bacterial infections. The optimal duration of intravenous antibiotic therapy is not clearly defined. Individuals usually receive intravenous antibiotics for 14 days, but treatment may range from 10 to 21 days. A shorter duration of antibiotic treatment risks inadequate clearance of infection which could lead to further lung damage. Prolonged courses of intravenous antibiotics are expensive and inconvenient. The risk of systemic side effects such as allergic reactions to antibiotics also increases with prolonged courses and the use of aminoglycosides requires frequent monitoring to minimise some of their side effects. However, some organisms which infect people with cystic fibrosis are known to be multi-resistant to antibiotics, and may require a longer course of treatment. This is an update of previously published reviews. OBJECTIVES:To assess the optimal duration of intravenous antibiotic therapy for treating chest exacerbations in people with cystic fibrosis. SEARCH METHODS:We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, abstract books and conference proceedings. Most recent search of the Group's Cystic Fibrosis Trials Register: 30 May 2019.We also searched online trials registries. Most recent search of the ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) portal: 06 January 2019. SELECTION CRITERIA:Randomised and quasi-randomised controlled trials comparing different durations of intravenous antibiotic courses for acute respiratory exacerbations in people with CF, either with the same drugs at the same dosage, the same drugs at a different dosage or frequency or different antibiotics altogether, including studies with additional therapeutic agents. DATA COLLECTION AND ANALYSIS:No eligible trials were identified for inclusion. A trial looking at the standardised treatment of pulmonary exacerbations is currently ongoing and will be included when the results are published. MAIN RESULTS: No eligible trials were included. AUTHORS' CONCLUSIONS:There are no clear guidelines on the optimum duration of intravenous antibiotic treatment. Duration of treatment is currently based on unit policies and response to treatment. Shorter duration of treatment should improve quality of life and adherence, result in a reduced incidence of drug reactions and be less costly. However, the shorter duration may not be sufficient to clear a chest infection and may result in an early recurrence of an exacerbation. This systematic review identifies the need for a multicentre, randomised controlled trial comparing different durations of intravenous antibiotic treatment as it has important clinical and financial implications. The currently ongoing STOP2 trial is expected to provide some guidance on these questions when published.
| S-EPMC6728060 | biostudies-literature
Project description:Acute kidney injury (AKI) is a common clinical condition among patients admitted in the hospitals. The condition is associated with both increased short-term and long-term mortality. With the development of a standardized definition for AKI and the acknowledgment of the impact of AKI on patient outcomes, there has been increased recognition of AKI. Two advances from past decades, the usage of computer decision support and the discovery of AKI biomarkers, have the ability to advance the diagnostic method to and further management of AKI. The increasingly widespread use of electronic health records across hospitals has substantially increased the amount of data available to investigators and has shown promise in advancing AKI research. In addition, progress in the finding and validation of different forms of biomarkers of AKI within diversified clinical environments and has provided information and insight on testing, etiology and further prognosis of AKI, leading to future of precision and personalized approach to AKI management. In this this article, we discussed the changing paradigms in AKI: from mechanisms to diagnostics, risk factors, and management of AKI.
| S-EPMC7230860 | biostudies-literature
Project description:We report trends in manifestations, treatment, and outcomes of 355 children with culture-confirmed melioidosis over 10 years at a pediatric hospital in northern Cambodia. Bacteremia and presentation with pneumonia were risk factors for death. A total of 39 children recovered after being given only oral antimicrobial drug treatment.
| S-EPMC8007301 | biostudies-literature
Project description: Not available
| S-EPMC4411634 | biostudies-literature
Project description:Immune cell infiltration in the tumor microenvironment is of prognostic and therapeutic import. These immune cell subsets can be heterogeneous and are composed of mature antigen-presenting cells, helper and effector cytotoxic T cells, toleragenic dendritic cells, tumor-associated macrophages, and regulatory T cells, among other cell types. With the development of novel drugs that target the immune system rather than the cancer cells, the tumor immune microenvironment is not only prognostic for overall patient outcome, but also predictive for likelihood of response to these immune-targeted therapies. Such therapies aim to reverse the cancer immunotolerance and trigger an effective antitumor immune response. Two major families of immunostimulatory drugs are currently in clinical development: pattern recognition receptor agonists (PRRago) and immunostimulatory monoclonal antibodies (ISmAb). Despite their immune-targeted design, these agents have so far been developed clinically as if they were typical anticancer drugs. Here, we review the limitations of this conventional approach, specifically addressing the shortcomings of the usual schedules of intravenous infusions every 2 or 3 weeks. If the new modalities of immunotherapy target specific immune cells within the tumor microenvironment, it might be preferable to deliver them locally into the tumor rather than systemically. There is preclinical and clinical evidence that a therapeutic systemic antitumor immune response can be generated upon intratumoral immunomodulation. Moreover, preclinical results have shown that therapeutic synergy can be obtained by combining PRRagos and ISmAbs to the local tumor site.
| S-EPMC3979477 | biostudies-literature
Project description:Supplementary Figure 1 and Supplementary Tables 1-4 have been re-uploaded so as to reflect the versions supplied during proofs stage. The publisher apologizes for the error in versioning. The HTML version of the paper has been updated.
| S-EPMC8329695 | biostudies-literature