Current challenges and unmet medical needs in myelodysplastic syndromes.
Ontology highlight
ABSTRACT:
SUBMITTER: Platzbecker U
PROVIDER: S-EPMC8324480 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Myelodysplastic syndromes (MDS) are a very heterogeneous disease, with extremely variable clinical features and outcomes. Current management relies on risk stratification based on IPSS and IPSS-R, which categorizes patients into low (LR-) and high-risk (HR-) MDS. Therapeutic strategies in LR-MDS patients mainly consist of erythropoiesis stimulating agents (ESAs), transfusion support, and luspatercept or lenalidomide for selected patients. Current unmet needs include the limited options available after treatment failure, and the consequent transfusion burden with several hospital admissions and poor quality of life. Therapeutic approaches in HR-MDS patients are aimed at changing the natural course of the disease and hypometylating agents (HMA) are the first choice. The only potentially curative treatment is allogeneic stem cell transplant (allo-HCT), restricted to a minority of young and fit candidates. Patients unfit for or those that relapse after the abovementioned options harbor an adverse prognosis, with limited overall survival and frequent leukemic evolution. Recent advances in genetic mutations and intracellular pathways that are relevant for MDS pathogenesis are improving disease risk stratification and highlighting therapeutic targets addressed by novel agents. Several drugs are under evaluation for LR and HR patients, which differ by their mechanism of action, reported efficacy, and phase of development. This review analyzes the current unmet clinical needs for MDS patients and provides a critical overview of the novel agents under development in this setting.
| S-EPMC9562187 | biostudies-literature
Project description:Invasive candidiasis (IC) is a serious infection caused by several Candida species, and the most common fungal disease in hospitals in high-income countries. Despite overall improvements in health systems and ICU care in the last few decades, as well as the development of different antifungals and microbiological techniques, mortality rates in IC have not substantially improved. The aim of this review is to summarize the main issues underlying the management of adults affected by IC, focusing on specific forms of the infection: IC developed by ICU patients, IC observed in haematological patients, breakthrough candidaemia, sanctuary site candidiasis, intra-abdominal infections and other challenging infections. Several key challenges need to be tackled to improve the clinical management and outcomes of IC patients. These include the lack of global epidemiological data for IC, the limitations of the diagnostic tests and risk scoring tools currently available, the absence of standardized effectiveness outcomes and long-term data for IC, the timing for the initiation of antifungal therapy and the limited recommendations on the optimal step-down therapy from echinocandins to azoles or the total duration of therapy. The availability of new compounds may overcome some of the challenges identified and increase the existing options for management of chronic Candida infections and ambulant patient treatments. However, early identification of patients that require antifungal therapy and treatment of sanctuary site infections remain a challenge and will require further innovations.
| S-EPMC10320127 | biostudies-literature
Project description:With the establishment of the immune surveillance mechanism since the 1950s, attempts have been made to activate the immune system for cancer treatment through the discovery of various cytokines or the development of antibodies up to now. The fruits of these efforts have contributed to the recognition of the 3rd generation of anticancer immunotherapy as the mainstream of cancer treatment. However, the limitations of cancer immunotherapy are also being recognized through the conceptual establishment of cold tumors recently, and colorectal cancer (CRC) has become a major issue from this therapeutic point of view. Here, it is emphasized that non-clinical strategies to overcome the immunosuppressive environment and clinical trials based on these basic investigations are being made on the journey to achieve better treatment outcomes for the treatment of cold CRC.
| S-EPMC9994045 | biostudies-literature
Project description:After being a neglected and poorly-understood disorder for many years, there has been a recent explosion of data regarding the complex pathogenesis of myelodysplastic syndromes (MDS). On the therapeutic front, the approval of azacitidine, decitabine, and lenalidomide in the last decade was a major breakthrough. Nonetheless, the responses to these agents are limited and most patients progress within 2 years. Allogeneic stem cell transplantation remains the only potentially curative therapy, but it is associated with significant toxicity and limited efficacy. Lack or loss of response after standard therapies is associated with dismal outcomes. Many unanswered questions remain regarding the optimal use of current therapies including patient selection, response prediction, therapy sequencing and combinations, and management of resistance. It is hoped that the improved understanding of the underpinnings of the complex mechanisms of pathogenesis will be translated into novel therapeutic approaches and better prognostic/predictive tools that would facilitate accurate risk-adaptive therapy.
| S-EPMC4124605 | biostudies-literature
Project description:Myelodysplastic syndromes (MDS) include a group of clonal myeloid neoplasms characterized by cytopenias due to ineffective hematopoiesis, abnormal blood and marrow cell morphology, and a risk of clonal evolution and progression to acute myeloid leukemia (AML). Because outcomes for patients with MDS are heterogeneous, individual risk stratification using tools such as the revised International Prognostic Scoring System (IPSS-R) is important in managing patients-including selecting candidates for allogeneic hematopoietic stem cell transplantation (ASCT), the only potentially curative therapy for MDS. The IPSS-R can be supplemented by molecular genetic testing, since certain gene mutations such as TP53 influence risk independent of established clinicopathological variables. For lower risk patients with symptomatic anemia, treatment with erythropoiesis-stimulating agents (ESAs) or lenalidomide (especially for those with deletion of chromosome 5q) can ameliorate symptoms. Some lower risk patients may be candidates for immunosuppressive therapy, thrombopoiesis-stimulating agents, or a DNA hypomethylating agent (HMA; azacitidine or decitabine). Among higher risk patients, transplant candidates should undergo ASCT as soon as possible, with HMAs useful as a bridge to transplant. Non-transplant candidates should initiate HMA therapy and continue if tolerated until disease progression. Supportive care with transfusions and antimicrobial drugs as needed remains important in all groups.
| S-EPMC5967332 | biostudies-literature
Project description:Triple negative breast cancer (TNBC) is an aggressive clinical phenotype characterized by lack of expression (or minimal expression) of estrogen receptor (ER) and progesterone receptor (PR) as well as an absence of human epidermal growth factor receptor-2 (HER2) overexpression. It shows substantial overlap with basal-type and BRCA1-related breast cancers, both of which also have aggressive clinical courses. However, this overlap is not complete, and the expression of ER, PR, and HER2 has been noted in basal-like tumors. TNBC also includes the normal-like subtype, and not all patients with TNBC harbor BRCA1 mutations. Because of its expression profile, TNBC is not amenable to treatment with hormone therapy or the anti-HER2 monoclonal antibody trastuzumab, and systemic treatment options are currently limited to cytotoxic chemotherapy. Overall survival, whether in early-stage or advanced disease, is poor compared with that in patients who have other phenotypes. A number of targeted approaches to TNBC are undergoing clinical evaluation, including the use of agents with poly(ADP-ribose) polymerase inhibitory properties such as iniparib (the United States Adopted Name for the investigational agent BSI-201), olaparib (AZD2281), and veliparib (ABT-888), antiangiogenic agents such as bevacizumab and sunitinib, and epidermal growth factor receptor blockers such as cetuximab and erlotinib. Encouraging results with some of these agents have been reported, thereby offering the promise for improved outcomes in patients with TNBC. The clinical characteristics of TNBC and clinical experience to date with novel targeted agents under development for this aggressive phenotype is reviewed.
| S-EPMC3244802 | biostudies-literature
Project description:Hemodiafiltration combines diffusive and convective solute removal in a single therapy by ultrafiltering 20% or more of the blood volume processed using a high-flux hemodialyzer and maintaining fluid balance by infusing sterile nonpyrogenic replacement fluid directly into the patient's blood. In online hemodiafiltration, the large volumes of replacement fluid required are obtained by online filtration of standard dialysate through a series of bacteria- and endotoxin-retaining filters. Currently available systems for online hemodiafiltration are on the basis of conventional dialysis machines with added features to safely prepare and infuse replacement fluid and closely control fluid balance. Hemodiafiltration provides greater removal of higher molecular weight uremic retention solutes than conventional high-flux hemodialysis, and recently completed randomized, controlled clinical trials suggest better patient survival with online hemodiafiltration compared with standard high-flux hemodialysis when a high convection volume is delivered. Hemodiafiltration is also associated with improvements in other clinical outcomes, such as a reduction in intradialytic hypotension, and it is now used routinely to treat >100,000 patients, mainly in Europe and Japan.
| S-EPMC6140578 | biostudies-literature
Project description:Despite the availability of effective inhaled therapies, many patients with asthma have poor asthma control. Uncontrolled asthma presents a significant burden on the patient and society, and, for many, remains largely preventable. There are numerous reasons why a patient may remain uncontrolled despite access to therapies, including incorrect inhaler technique, poor adherence to treatment, oversight of triggers and suboptimal medical care. Shared decision-making, good patient-clinician communication, supported self-management, multidisciplinary patient education, new technology and risk stratification may all provide solutions to this major unmet need in asthma. Novel treatments such as biologics could benefit patients' lives, while the investigations into biomarkers, non-Type 2 asthma, treatable traits and disease modification give an exciting glimpse into the future of asthma care.
| S-EPMC9488919 | biostudies-literature
Project description:Unmet medical needs refer to the state where a patient's medical care or service is insufficient, inadequate, or lacking. Numerous factors influence unmet medical needs. We used a multi-pronged approach to explore the factors influencing unmet medical needs in the Korean health care system according to Anderson's Behavioral Model of Health Services Use. To this end, we used data from 11,378 adults over 19 years old in the 2016 Korea Health Panel Survey and performed multiple logistic regression analyses. The odds of experiencing unmet medical needs were significantly greater among older participants (odds ratio (OR) = 2.51, 95% confidence interval (CI) = 1.78-3.56); low-income participants (OR = 1.41, 95% CI = 1.14-1.75); non-workers (OR = 1.24, 95% CI = 1.06-1.46); those who had received non-covered treatment (OR = 1.24, 95% CI = 1.08-1.42); those who did not regularly exercise (OR = 1.23, 95% CI = 1.02-1.48); and those experiencing pain (OR = 2.29, 95% CI = 1.97-2.66), worse self-rated health status (OR = 2.29, 95% CI = 1.89-2.79), and severe depression (OR = 2.46, 95% CI = 1.39-4.35). About one in ten Korean citizens (11.60%) have unmet medical service needs. Policies that strengthen coverage for physically and economically vulnerable groups are needed.
| S-EPMC6651044 | biostudies-literature
Project description:This study aimed to analyze the factors affecting the unmet medical needs of patients with benign prostate enlargement (BPE) based on Andersen's behavioral model. The data were taken from the 2009-2016 Korea Health Panel Study and 3003 participants were used for analysis. "Unmet medical needs" was used as a dependent variable. Independent variables were predisposing variables: age, educational attainment, and marital status; enabling factors: income, job type, and insurance type; and need factors: lying in a sickbed, activity limitation, subjective health status, and having chronic diseases. Results showed that younger patients experienced a higher probability of unmet medical needs. Those with higher educational attainment had a lower chance of experiencing unmet medical needs. Patients with national health insurance were less likely to experience unmet medical needs. In addition, patients who experienced lying in a sickbed had a higher probability of experiencing unmet medical needs. Therefore, in order to reduce the unmet medical needs of patients with BPE, it is necessary to allow patients to be treated early and give them accurate information about the disease. In addition, access to medical care should be strengthened through continuous care focused on primary care.
| S-EPMC7230821 | biostudies-literature