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BMJ Case Reports Mar 2022Cryptococcal species endocarditis is infrequently described, carries high mortality and nearly always occurs in immunocompromised states or on prosthetic valves. We...
Cryptococcal species endocarditis is infrequently described, carries high mortality and nearly always occurs in immunocompromised states or on prosthetic valves. We report the case of a man in his 70s with multiple recent hospitalisations for pneumonia, hypercalcaemia and septic tank exposure who presented with intermittent fevers, progressive weakness,and worsening encephalopathy, manifested as confusion and word-finding difficulties for 3 weeks. Workup revealed cryptococcal species on blood serum gram stain, native aortic valve endocarditis and meningitis. Cerebrospinal fluid analysis demonstrated lymphocytosis, ultimately found to be secondary to chronic lymphocytic leukaemia. Surgical valve replacement was deemed medically contraindicated and antifungal therapy was initiated. Though poorly understood with very few documented cases, management of cryptococcal endocarditis relies on prompt diagnosis, early surgery when indicated, long-term antifungal therapy and treatment of underlying immunocompromising states where possible.
Topics: Antifungal Agents; Cryptococcosis; Cryptococcus; Cryptococcus neoformans; Endocarditis; Humans; Immunocompromised Host; Meningitis; Meningitis, Cryptococcal
PubMed: 35236688
DOI: 10.1136/bcr-2021-247310 -
Journal of Fungi (Basel, Switzerland) Mar 2021Recent outbreaks of (CG) infections in North America have sparked renewed interest in the pathogenic potential of CG, and have underscored notable differences with in... (Review)
Review
Recent outbreaks of (CG) infections in North America have sparked renewed interest in the pathogenic potential of CG, and have underscored notable differences with in terms of geographic distribution, pathogen virulence, and host susceptibility. While cases of CG are increasingly reported in patients with a wide variety of underlying conditions, only very few have been reported in patients with lymphoid neoplasms. Herein, we report a case of autochthonous CG meningitis in a patient receiving ibrutinib for chronic lymphocytic leukemia in France, and review available data on the clinical epidemiology of CG infections in patients with lymphoid neoplasms. We also summarise recent data on the host responses to CG infection, as well as the potential management pitfalls associated with its treatment in the haematological setting. The clinical epidemiology, clinical presentation, and course of disease during infections caused by CG involve complex interactions between environmental exposure to CG, infecting genotype, pathogen virulence factors, host susceptibility, and host immune responses. Future treatment guidelines should address the challenges associated with the management of antifungal treatments in the onco-haematological setting and the potential drug-drug interactions.
PubMed: 33809570
DOI: 10.3390/jof7030212 -
Mycoses Aug 2022The epidemiology of fungal infections in Eritrea is unknown. Most cases are under-reported due to a lack of diagnostics. This study estimates the burden of serious...
The epidemiology of fungal infections in Eritrea is unknown. Most cases are under-reported due to a lack of diagnostics. This study estimates the burden of serious fungal infections and highlights treatment and diagnostic gaps in the country. All publications related to fungal infections were identified by searches using PubMed/Medline and Google Scholar. Where no data were available, data from neighbouring countries, then sub-Saharan African countries, then other parts of the world were considered for deriving estimates. The Eritrea population was 3,546,427 in 2020. In 2020, HIV/AIDS patients numbered 1400 and TB incidence were 2875. The five-year adult prevalence of asthma (2016-2020) was 41,390, and the total prevalence estimate of chronic obstructive pulmonary disease (COPD) was 308,328. The annual incidence of cryptococcal meningitis and Pneumocystis jirovecii pneumonia in AIDS patients was estimated at 96 and 205 cases. Oesophageal candidiasis incidence is 715 HIV-infected patients. Chronic pulmonary aspergillosis prevalence, including post-tuberculosis cases, was estimated at 1399 (39/100,000). Fungal asthma has a prevalence of 1035 and 1366 in adults. The estimated prevalence of recurrent vulvovaginal candidiasis and tinea capitis is 59,391 and 342,585, respectively. There are no data on candidaemia, but it is estimated at 5/100,000 (177 cases annually). Invasive aspergillosis in leukaemia, lung cancer, COPD and HIV is estimated at 540 cases and fungal keratitis in 514 cases annually. Serious fungal infections are prevalent in Eritrea with approximately 408,164 people (11.5%) affected annually. Studies on fungal diseases to improve diagnosis and treatment are required with the implementation of a national surveillance program.
Topics: Acquired Immunodeficiency Syndrome; Adult; Asthma; Eritrea; Humans; Incidence; Mycoses; Prevalence; Pulmonary Disease, Chronic Obstructive
PubMed: 35633079
DOI: 10.1111/myc.13474 -
Blood Cancer Discovery Jan 2022Central nervous system (CNS) dissemination of B-precursor acute lymphoblastic leukemia (B-ALL) has poor prognosis and remains a therapeutic challenge. Here we performed...
Central nervous system (CNS) dissemination of B-precursor acute lymphoblastic leukemia (B-ALL) has poor prognosis and remains a therapeutic challenge. Here we performed targeted DNA sequencing as well as transcriptional and proteomic profiling of paired leukemia-infiltrating cells in the bone marrow (BM) and CNS of xenografts. Genes governing mRNA translation were upregulated in CNS leukemia, and subclonal genetic profiling confirmed this in both BM-concordant and BM-discordant CNS mutational populations. CNS leukemia cells were exquisitely sensitive to the translation inhibitor omacetaxine mepesuccinate, which reduced xenograft leptomeningeal disease burden. Proteomics demonstrated greater abundance of secreted proteins in CNS-infiltrating cells, including complement component 3 (C3), and drug targeting of C3 influenced CNS disease in xenografts. CNS-infiltrating cells also exhibited selection for stemness traits and metabolic reprogramming. Overall, our study identifies targeting of mRNA translation as a potential therapeutic approach for B-ALL leptomeningeal disease. SIGNIFICANCE: Cancer metastases are often driven by distinct subclones with unique biological properties. Here we show that in B-ALL CNS disease, the leptomeningeal environment selects for cells with unique functional dependencies. Pharmacologic inhibition of mRNA translation signaling treats CNS disease and offers a new therapeutic approach for this condition..
Topics: Central Nervous System; Central Nervous System Diseases; Central Nervous System Neoplasms; Humans; Meningeal Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Biosynthesis; Proteomics
PubMed: 35019858
DOI: 10.1158/2643-3230.BCD-20-0216 -
Annals of Oncology : Official Journal... Oct 1996Carcinomatous meningitis (CM) is an uncommon but devastating complication of malignancy. The management is controversial and clear recommendations cannot be made... (Review)
Review
Carcinomatous meningitis (CM) is an uncommon but devastating complication of malignancy. The management is controversial and clear recommendations cannot be made because: 1) Most series include patients with CM that has arisen from different primary malignancies which are associated with different median survival intervals. 2) There have been no prospective randomised investigations of treatment modalities in patients with CM from a particular tumour type. 3) The definition of response varies from one report to another so that some response rates refer to cytological changes in the CSF while others take clinical, cytological and biochemical parameters into account. 4) Reports include patients with and without parenchymal metastases and the natural history of carcinomatous meningitis in the two situations may differ. The median survival of solid tumour carcinomatous meningitis (excluding leukaemia and lymphoma) is approximately 2-3 months and patients with breast cancer have the longest survival (median 3 months). Currently patients are treated with radiotherapy to part or all of the neuraxis with either intrathecal or intravenous chemotherapy but the relative contribution of these modalities to survival or quality of life remains unknown. Approximately 50% of patients with carcinomatous meningitis die from other causes, including systemic disease. The two most important endpoints for the patient, neurological improvement and overall survival, are seldom used in isolation in the literature. Many reports have focused on surrogate markers of response, namely biochemical and cytological data points but the correlation between clinical status and these parameters is poor because of differences between lumbar and ventricular CSF and disturbances of CSF flow in CM. The current literature does not provide clear guidelines for the treatment of this condition. Multicentre, prospective, randomised trials should be conducted that address questions of most relevance to the patient, namely neurological status and overall survival.
Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Humans; Meningeal Neoplasms; Meningitis; Neoplasms; Prognosis; Survival Rate
PubMed: 8922190
DOI: 10.1093/oxfordjournals.annonc.a010755 -
Canadian Medical Association Journal Jan 1981Acute lymphocytic leukemia is the most common cancer of childhood. A series of total therapy studies begun in 1962 at St. Jude Children's Research Hospital in Memphis,... (Clinical Trial)
Clinical Trial Review
Acute lymphocytic leukemia is the most common cancer of childhood. A series of total therapy studies begun in 1962 at St. Jude Children's Research Hospital in Memphis, Tennessee has had a dramatic impact on the survival of children with this disease. These studies have systematically examined various drug combinations and radiation therapy in an effort to cure acute lymphocytic leukemia. As a result, a once uniformly fatal condition is now curable in nearly one half of cases. In addition to improved control of the primary disease, refinements in drug treatment and in supportive care have diminished the frequency of severe infections, which may complicate aggressive therapy. Although the quality of life for the survivors so far appears generally good, treatment-induced toxic effects may impose subtle, though significant, handicaps in some cases. A combination of clinical and laboratory investigations begun in the mid-1970s is beginning to demonstrate a previously unknown heterogeneity among patients with acute lymphocytic leukemia. It is now possible to recognize a substantial minority of patients on the basis of these studies as being at "high risk" for treatment failure. For them, drastic modifications of present programs are being investigated in an attempt to improve their prognosis. For patients lacking high-risk features improvements are still needed, but changes in their treatment must be kept within the framework of what is presently successful and must address the hazard of long-term toxicity.
Topics: Adolescent; Antineoplastic Agents; Bone Marrow; Bone Marrow Transplantation; Child; Child, Preschool; Clinical Trials as Topic; Drug Resistance; Drug Therapy, Combination; Female; Humans; Infant; Leukemia, Lymphoid; Leukocyte Count; Male; Meningeal Neoplasms; Prognosis; Transplantation, Homologous
PubMed: 7006781
DOI: No ID Found -
Expert Opinion on Drug Delivery Dec 2010Cytarabine is a polar nucleoside drug used for the treatment of myeloid leukemia and non-Hodgkin's lymphoma. The drug has a short plasma half-life, low stability and... (Review)
Review
IMPORTANCE OF THE FIELD
Cytarabine is a polar nucleoside drug used for the treatment of myeloid leukemia and non-Hodgkin's lymphoma. The drug has a short plasma half-life, low stability and limited bioavailability. Overdosing of patients with continuous infusions may lead to side effects. Thus, various prodrug strategies and delivery systems have been explored extensively to enhance the half-life, stability and delivery of cytarabine. Among the recent cytarabine prodrugs, amino acid conjugate ValCytarabine and fatty acid derivative CP-4055 (in Phase III trials) have been investigated for the treatment of leukemia and solid tumors, respectively. Alternatively, delivery systems of cytarabine have emerged for the treatment of different cancers. The liposomal-cytarabine formulation (DepoCyt®, Pacira Pharmaceuticals Inc., New Jersey, USA) has been approved for the treatment of lymphomatous meningitis.
AREAS COVERED IN THIS REVIEW
Various prodrug strategies evaluated for cytarabine are discussed. Then, the review summarizes the drug delivery systems that have been used for more effective cancer therapy.
WHAT THE READER WILL GAIN
This review provides in-depth discussion of the prodrug strategy and delivery systems of cytarabine derivatives for the treatment of cancer. The design of cytarabine prodrugs and delivery systems provides insights for designing the next generation of more effective anticancer agents with enhanced delivery and stability.
TAKE HOME MESSAGE
Strategies on designing cytarabine prodrug and delivery formulations showed great promise in developing effective anticancer agents with better therapeutic profile. Similar studies with other anticancer nucleosides can be an alternative approach to gaining access to more effective anticancer agents.
Topics: Antineoplastic Agents; Cytarabine; Drug Delivery Systems; Humans; Leukemia; Lymphoma, Non-Hodgkin; Prodrugs
PubMed: 20964588
DOI: 10.1517/17425247.2010.527330 -
Journal of Neurosurgery. Case Lessons Jun 2021Acute promyelocytic leukemia (APL) has long been associated with coagulation disorders. The proposed mechanism is a combination of fibrinolysis, proteolysis, platelet...
Concomitant central venous sinus thrombosis and subdural hematoma in acute promyelocytic leukemia: middle meningeal artery embolization enables safe anticoagulation. Illustrative case.
BACKGROUND
Acute promyelocytic leukemia (APL) has long been associated with coagulation disorders. The proposed mechanism is a combination of fibrinolysis, proteolysis, platelet dysfunction, thrombocytopenia, and possibly disseminated intravascular coagulation. Hemorrhagic complications are prominent.
OBSERVATIONS
In this case, a 25-year-old female with newly diagnosed APL developed extensive cerebral venous thrombosis (CVT) and was initiated on a protocol with idarubicin and all- retinoic acid. The general recommendation for treating CVT is anticoagulation to stabilize the existing thrombus and prevent propagation. The patient was initiated on a heparin drip, but her clinical course was complicated by subdural hemorrhage (SDH) and epidural hemorrhage in the setting of thrombocytopenia. Anticoagulation was held, and her CVT propagated on follow-up imaging. To restart anticoagulation for CVT with a limited risk of SDH, the authors pursued middle meningeal artery (MMA) embolization. The patient was transitioned to apixaban and discharged to home.
LESSONS
MMA embolization enables safe anticoagulation in patients with concomitant CVT and SDH. The authors report the complex clinical course and effective management of this rare clinical scenario.
PubMed: 36046512
DOI: 10.3171/CASE2080 -
Therapeutic Advances in Infectious... 2021Azerbaijan is an upper middle-income country in South Caucasus with an area of 86,600 km and a total population of 10 million people and gross domestic product of...
BACKGROUND
Azerbaijan is an upper middle-income country in South Caucasus with an area of 86,600 km and a total population of 10 million people and gross domestic product of US $4480 per capita. The aim of this research is to estimate fungal infection burden and highlight the problem at national and international levels.
METHODS
Fungal infection burden was estimated using data from epidemiological papers and population at risk and LIFE (Leading International Fungal Education) modelling.
RESULTS
The number of people living with human immunodeficiency virus (PLHIV) in 2018 was 6193, 29% of them not receiving antiretroviral therapy. Based on 90% and 20% rates of oral and oesophageal candidiasis in patients with CD4 cell count <200 µl we estimate 808 and 579 patients with oral and oesophageal candidiasis, respectively. The annual incidences of cryptococcal meningitis and Pneumocystis pneumonia are 5 and 55 cases, respectively. We estimated 2307 cases of chronic pulmonary aspergillosis (CPA), 4927 patients with allergic bronchopulmonary aspergillosis (ABPA), and 6504 with severe asthma with fungal sensitization (SAFS). Using data on chronic obstructive pulmonary diseases (COPD), lung cancer, acute myeloid leukaemia rates, and number of transplantations, we estimated 693 cases of invasive aspergillosis following these conditions. Using a low-European rate for invasive candidiasis, we estimated 499 and 75 patients with candidemia and intra-abdominal candidiasis respectively. The number of adult women (15-55 years) in Azerbaijan is ~2,658,000, so it was estimated that 159,490 women suffer from recurrent vulvovaginal candidiasis (rVVC).
DISCUSSION
In total, the estimated number of people suffering from fungal diseases in Azerbaijan is 225,974 (2.3% of the population). However, the fungal rate is underestimated due to lack of epidemiological data. The most imminent need is improvement in diagnostic capabilities. This aim should be achieved establishing a reference laboratory and equipping major clinical centers with essential diagnostics assays.
PubMed: 34497715
DOI: 10.1177/20499361211043969 -
Journal of Clinical Medicine May 2015Myeloid sarcoma (MS) of the central nervous system (CNS) is a rare presentation of leukemic mass infiltration outside of the bone marrow. It may involve the... (Review)
Review
Myeloid sarcoma (MS) of the central nervous system (CNS) is a rare presentation of leukemic mass infiltration outside of the bone marrow. It may involve the subperiosteum and dura mater and, on rare occasions, can also invade the brain parenchyma. The disease is most commonly seen in children or young adults; however, it has been described in multiple age groups. MS can be seen in patients with acute myeloid leukemia (AML), chronic myeloid leukemia and other myeloproliferative disorders. This entity has the potential to be underdiagnosed if the MS appearance precedes the first diagnosis of leukemia. The main reason is that their appearance on CT and MRI has a broad differential diagnosis, and proper diagnosis of MS can only be made if the imaging findings are correlated with the clinical history and laboratory findings. Herein, we describe the intracranial CNS manifestations of MS in patients with AML on CT and MRI involving the brain and/or meninges. This study is based on a systematic review of the literature. In addition, three case reports from the author's institution with AML and intracranial involvement of MS are included. Our aim is to enhance the awareness of this entity among both clinicians and radiologists.
PubMed: 26239467
DOI: 10.3390/jcm4051102